CN102853946B - Monitor thermo-responsive article and add up the method for received heat and the indicator of use thereof - Google Patents
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Abstract
The present invention relates to monitor thermo-responsive article and add up the method for received heat and the indicator of use thereof.The present invention monitors the method for thermo-responsive article received heat and comprises the following steps: (a) provides thermo-responsive article；(b) certain area one layer of volatile dye of attachment on these thermo-responsive article；C () adheres to one layer of adsorbing material in this volatile dye；D () adheres to diaphragm seal at above-mentioned certain area and periphery thereof, this diaphragm seal makes described sorbing material layer and the sealing of volatile dye layer be attached on described thermo-responsive article；Wherein, described volatile dye can be volatilized under heating condition, described adsorbing material irreversibly adsorbs volatilized dyestuff, and the color of volatile dye layer takes off the being proportionate property of volatile quantity of variable and dyestuff, the being proportionate property of heat that the latter is absorbed with thermo-responsive article again.The inventive method and the time temperature indicator provided according to these methods can indicate situation of being heated and the quality state of thermo-responsive article effectively.
Description
Technical field
The invention belongs to field of material technology, be directed to use with heat-sensitive material to monitor thermo-responsive article and add up received heat
Method.Specifically, the present invention relates to the use of the volatilization character Production Time-thermindicator of material, by being heated-volatilize-
The material transfer process of absorption, it is achieved the change of indicator feature site color, display uses the thing of this time-temperature indicator
Whether the most thermo-responsive article of product excessively go bad because being heated or lost efficacy.
Background technology
Some stability article highstrung to temperature or product needed store at low temperatures or transport, such as major part epidemic disease
Seedling, biological product, biological activity sample and a part of medicine etc., and such as fresh food such as fresh milk, milk product, fresh meat, fresh fish
Deng.For a long time, mark effect duration or freshness date are to ensure that the master that these goods/products particularly medicine or food safety use
Want method, but whether the medicine that these methods often cannot reflect those to need under cryogenic to store and transport or food exist
The long time is exposed at a temperature of exceeding safety in transportation and storage.The method using cheap and simple accurately indicates various thermo-responsive article such as
Need whether the fresh food of low temperature storage, vaccine (how between 2 DEG C～8 DEG C), biological activity sample etc. are storing or transport
During go bad because exceeding safety in transportation and storage temperature, lost efficacy or inactivate, it can be made to use safety and effect to obtain preferably
Ensure.
Last century the nineties, World Health Organization (WHO) (WHO) begins to focus on vaccine and is heated in cold chain storage and transport process excessively
Problem, because this can cause the immune effect of vaccine to decline, thus reduces the protective effect of vaccine.Subsequently, WHO appeals exploitation one
Plant label easy to use, with low cost, to accurately reflect vaccine after manufacture is dispatched from the factory through transport and storage arrival terminal use
During the accumulative history being heated.Basic demand to this label is as follows: 1, can accurately indicate vaccine whether to be heated excessively thus
Limit and use the excessive vaccine that is heated；2, volume is little, can paste on vaccine bottle, ampoule bottle, syringe；3, from producing to reality
Use whole during reliable and stable；4, it is suitable for large-scale production, with low cost, United Nations Children's Fund can be met
(UNICEF) whole world vaccine demand.
1996, first company's (predecessor is Lifelines) of one entitled TempTime of the U.S. was developed to meet WHO
The label required, and it is applied to tri-vaccine manufacturer productions of GlaxoSmithKline, Sanofi-Pasteur and Novartis
Polio vaccine.The label of Temptime company supply mainly has three classes according to use function.The first kind is stagnation temperature
Degree indicator (Critical Temperature Indicator, CTI), this kind of label is the most vertical once exceed setting value in temperature
I.e. variable color.Equations of The Second Kind be so-called critical temperature-time marker (Critical Temperature-Time Indicator,
CTTI), the color change of this label has postponed, be exposed to set the above several minutes of temperature or several tens minutes after variable color.
The response time of the 3rd class label needs longer, referred to as time-temperature indicator (Time-Temperature
Indicator, TTI), it is that temperature sensing material accepts just variable color after the heat of specified quantitative, this kind of label is only and is suitable for instruction vaccine
The label of thermal histories.
At present, patent about this time-temperature indicator has had up to a hundred in the world.These patented technologies according to
The operation principle of product, can be divided into mechanical type, chemical type, enzyme reaction type, microbiocidal, polymer-type, electron chemistry type and
Diffused etc..These technology are mainly based upon the engineering properties of material, electrical property, scattering nature, enzyme reaction, polyreaction
Three classes are mainly had: polymer-type, enzyme reaction type and diffused on, the TTI label of comparative maturity and commercialization.
Polymer-type is developed by TempTime company of the U.S., is mainly based upon replacement diacetylene derivant and passes through solid-state
Isosorbide-5-Nitrae-polyaddition reaction, generates coloured polymer.The speed of this polyreaction is accelerated with the rising of temperature, generation
Polymer makes color constantly deepen, by with periphery color contrast, may indicate that whether vaccine is heated excessively.This labeling requirement
Screening synthesis is suitably polymerized monomer, and label make after need to preserve at a temperature of even lower at-18 DEG C.
An enzyme reaction type indicator substantially class pH value indicator in early days, it is by measuring enzymatic lipid substrate
Hydrolysis release proton H+, causes the pH value of medium to change, thus causes the change of color, instruction temperature or thermal histories.Enzymatic
Hydrolysis raises with temperature and accelerates, and the most therefore the rate of release of proton is accelerated.Representative is a company of Sweden
The Vitsab ring indicator developed.
The mainstream product of diffused time-temperature indicator more in early days is the 3M Monitor that Minnesota Mining and Manufacturing Company produces
Mark board indicator, it depends on the type of dyestuff based on dyestuff diffusion on cord, temperature indicating range and response phase.Separately
The diffused indicator of a kind of form is to be applied on porous matrix by the material of specific fusing point, and the optical index of the two is close.
When the material of coating is melt above in specific temperature and is diffused in porous matrix, after discharging the air in substrate hole, substrate
Light transmittance increase, thus also can realize the change of color, show thermal histories.
At present, nearly 20 kinds vaccines of WHO are divided into 4 classes according to its thermal stability: least stabilization of vaccines, unstable epidemic disease
Seedling, stabilization of vaccines and high stability vaccine, and the product technology requirement to corresponding time-temperature indicator is proposed accordingly.According to
This technical standard formulated considers the performance of existing indicator product, and non-fully with the thermal stability of vaccine itself for depending on
According to.It is true that in needing nearly 20 kinds of vaccines of cold chain accumulating monitored over time, the heat stability of every kind of vaccine is to differ
, preferable time-temperature indicator should be that the individualized time-temperature of the indicated product thermal stability of fully reflection refers to
Show device, i.e. speed and the temperature effects thereof of color change are tried one's best consistent with indicated product failure process.
To this end, this area expects have a kind of can be used for monitor the method that thermo-responsive article add up received heat, expect this side
Method, when the accumulating monitoring of thermo-responsive article, could be aware that whether its accumulative received heat exceeds the scope that people expect to control.
Summary of the invention
It is an object of the invention to provide and a kind of simply, effectively can be used for monitoring thermo-responsive article and add up the side of received heat
Method, this method, when the storage and transport process monitoring of thermo-responsive article, may indicate that whether its accumulative received heat is beyond people's phase
Scope to be controlled.The present inventor will have certain color and have volatile material (can be described as in this article volatility dye
Material) it is attached on thermo-responsive article, outside this volatile dye, adhere to the adsorbent of one layer of adsorbable described dyestuff, re-use one
Described volatile dye layer and adsorbent layer are sealed on these thermo-responsive article by individual sealant；So, thermo-responsive at this
In the storage and transport process of article, volatile dye absorbs heat and volatilizees and be adsorbed the absorption of material layer, and the volatile quantity of dyestuff is with accumulative
Heat (relevant to the degradation speed of thermo-responsive article or degree) the being proportionate property absorbed；Come for concrete thermo-responsive article
Select the kind of dyestuff and consumption and combine the speed of other method regulation and control dyestuff volatilization；According to one embodiment of the invention
Dye coating because heat absorption volatilization and lighter, dye coating variable color response almost can be complete with the activity change of thermo-responsive article
Unanimously, thus can be readily determined whether thermo-responsive article are in effect duration or goods simply by the change of dye coating color
In the frame phase.The present invention is accomplished based on above-mentioned discovery.
To this end, first aspect present invention provides and a kind of monitors the method that thermo-responsive article add up received heat, the method bag
Include following steps: (a) provides thermo-responsive article；(b) certain area one layer of volatile dye of attachment on these thermo-responsive article；
C () adheres to one layer of adsorbing material in this volatile dye；D () adheres to diaphragm seal at above-mentioned certain area and periphery thereof, this is close
Sealer makes described sorbing material layer and the sealing of volatile dye layer be attached on described thermo-responsive article；Wherein, described volatility
Dyestuff can volatilize under heating condition, and described adsorbing material irreversibly adsorbs volatilized dyestuff, and volatile dye layer
Color take off the being proportionate property of volatile quantity of variable and dyestuff, the heat that the latter is absorbed with thermo-responsive article again is proportionate
Property.
Based on first aspect present invention, second aspect present invention provides a kind of quality state monitoring thermo-responsive article
Method.
Based on first aspect present invention, third aspect present invention provides a kind of monitors the side whether thermo-responsive article lost efficacy
Method.
Based on first aspect present invention, fourth aspect present invention provides a kind of time-temperature indicator, and it is included in and makes
With before in separate indicated work ergosphere with two part of adsorption function layer.
Based on first aspect present invention, fifth aspect present invention provides a kind of use first aspect present invention, second party
The thermo-responsive article of method monitoring described in face or the third aspect.
Based on first aspect present invention, sixth aspect present invention provides a kind of when using described in fourth aspect present invention
M-thermindicator is monitored received heat, monitoring quality state or monitors whether the thermo-responsive article lost efficacy.
Based on first aspect present invention, seventh aspect present invention provides a kind of thermo-responsive article, and it includes thermo-responsive thing
Product body, and time-temperature indicator adhered thereto, described time-temperature indicator includes indicated work ergosphere and suction
Two parts of attached functional layer.
Based on first aspect present invention, eighth aspect present invention provides compound of formula I, and it can be as the volatilization of the present invention
Property dyestuff use:
Based on first aspect present invention, ninth aspect present invention provides the purposes of eighth aspect present invention compound of formula I,
For monitoring the accumulative received heat of thermo-responsive article, monitoring quality state and/or whether losing efficacy；Or for first party of the present invention
The volatile dye of method described in face, second aspect or the third aspect；Or for Time-temperature described in fourth aspect present invention
The volatile dye layer of indicator；Or the volatile dye layer for thermo-responsive article described in seventh aspect present invention.
Accompanying drawing explanation
Fig. 1 is the structural representation of a kind of time-temperature indicator that the embodiment of the present invention makes.
Fig. 2 A is that a kind of time-temperature indicator that the embodiment of the present invention makes uses and colourshifting process schematic diagram.Fig. 2 B
It is the use observed from another angle of a kind of time-temperature indicator that makes of the embodiment of the present invention and colourshifting process schematic diagram.
Fig. 3 is a kind of time-temperature indicator that the embodiment of the present invention 1 uses that dyestuff A makes as temperature-sensitive functional material
Use and colourshifting process design sketch.
Fig. 4 a and Fig. 4 b is the Time-temperature instruction that the embodiment of the present invention 2 uses that dyestuff A makes as temperature-sensitive functional material
Device color change at different temperatures.
Fig. 5 is the time-temperature indicator that the embodiment of the present invention 2 uses that dyestuff A makes as temperature-sensitive functional material, with color
Difference Δ E* abThe activation energy of=10 colourshifting process tried to achieve as the terminal of variable color.
Fig. 6 is that the embodiment of the present invention 2 uses dyestuff A as temperature-sensitive functional material, sets for a kind of Hepatitis B virus vaccine (Hep-B)
The time-temperature indicator that meter makes, its variable color response is the most completely the same with the activity change of vaccine.
Fig. 7 is that the embodiment of the present invention 3 uses dyestuff A as temperature-sensitive functional material, uses different inks (i.e. dyestuff) dense
Spend the initial chromatic value of the indicator made with identical inking amount, and colourshifting process at the same temperature.
Fig. 8 is that the embodiment of the present invention 3 uses dyestuff A as temperature-sensitive functional material, uses different bodies with identical
The indicator that inking amount makes, the amount of the temperature-sensitive functional material that the time that indicator is reached home prints with unit are is linearly
Relation.
Fig. 9 is that the embodiment of the present invention 4 uses three kinds of compound of formula I (respectively dyestuff A, B, C) to indicate as Time-temperature
The thermo-sensitive material of device, the indicator of making aberration at 50 DEG C is over time.
Figure 10 is that the embodiment of the present invention 5 uses hexamethylene, dichloromethane, methyl acetate, ethanol, ethyl acetate conduct respectively
Solvent printing dyestuff A is as temperature-sensitive functional material, and the aberration of indicator is over time at the same temperature.
Figure 11 is that the embodiment of the present invention 6 adds appropriate binding agent EC (ethyl cellulose) in the organic solution of dyestuff A,
The indicator made is chromatic aberration and the relation of time at 80 DEG C.
Figure 12 be the embodiment of the present invention 7 with dyestuff B for temperature-sensitive functional material, when selecting three kinds of different adsorbing materials to make
M-thermindicator, under identical temperature environment, the indicated work ergosphere aberration of indicator is over time.
Some terms and reference thereof that the present invention uses are summarized as follows:
Indicated work ergosphere 1, the second release film layer 11, volatile dye layer 15, sorbing material layer 21,
Adsorption function layer 2, non-drying glue layer 12, reference color layer 16, non-drying glue layer 22,
Thermo-responsive article 3, diaphragm seal layer 13, the first release film layer 17, release film layer 23,
Substrate material layer 10, sealant layer 14, substrate material layer 20, sealing coat 24.
Detailed description of the invention
First aspect present invention provides a kind of monitors the method that thermo-responsive article add up received heat, and the method includes following
Step:
A () provides thermo-responsive article；
(b) certain area one layer of volatile dye of attachment on these thermo-responsive article；
C () adheres to one layer of adsorbing material in this volatile dye；
D () adheres to diaphragm seal at above-mentioned certain area and periphery thereof, this diaphragm seal makes described sorbing material layer and volatility
Dye coating seals and is attached on described thermo-responsive article；
Wherein, described volatile dye (such as under the temperature conditions that expectation is disposed, such as, is being expected under heating condition
Storage and/or transport temperature conditions under, such as disposing in the case of temperature surprisingly raises, such as, expecting in accelerated test
Disposal temperature conditions under, such as in the case of accelerated test desired disposal temperature is 25 DEG C and/or 37 DEG C) can volatilize,
Described adsorbing material irreversibly adsorbs volatilized dyestuff, and the color of volatile dye layer takes off variable (CF, amount
Of color fading) and the being proportionate property of volatile quantity of dyestuff, the heat that the latter is absorbed with thermo-responsive article again is positive
Guan Xing.
Method described according to a first aspect of the present invention, wherein monitors thermo-responsive article and adds up received heat volatile dye
The color of layer takes off variable and/or color takes off variable Rate and characterizes.In one embodiment, this color take off variable can be further with waving
The aberration Δ E of the property sent out dye coating* abChange characterize；In one embodiment, the color of volatile dye layer take off variable Rate can
By the chromatic aberration scope set divided by the time representation reached needed for described chromatic aberration scope；In one embodiment,
Color takes off variable Rate variation with temperature obeys Arrhenius equation, can be with the activation energy obtained by the equationaCharacterize.
Method described according to a first aspect of the present invention, wherein said thermo-responsive article are to need at-40 DEG C to 50 DEG C
Storage and/or the article of transport, preferably need at-30 DEG C to 40 DEG C of storages and/or the article of transport, preferably need-
30 DEG C to 30 DEG C storages and/or the article of transport, preferably need at-20 DEG C to 20 DEG C of storages and/or the article of transport, preferably
It is to need at-20 DEG C to 10 DEG C of storages and/or the article of transport, such as, to need at-10 DEG C to 10 DEG C of storages and/or the thing of transport
Product, such as, need at 0 DEG C to 10 DEG C of storage and/or the article of transport, such as, to need at 2 DEG C to 8 DEG C of storages and/or the thing of transport
Product.In one embodiment, described thermo-responsive article include but not limited to: vaccine is (such as to heat-labile vaccine, example
Such as polio vaccine, antityphoid vaccine, Hepatitis B virus vaccine etc.), (such as human normal immunoglobulin, anti-human T cell pig exempts from biological product
Epidemic disease globulin etc.), biological activity sample (such as blood plasma, whole blood, serum etc.), medicine (such as posterior pituitary injection, injection
Stannous etifenin etc.), food (such as fresh meat, fresh fish etc.), beverage (such as fresh milk, milk product, Yoghourt, pasturising milk)
Deng.
Method described according to a first aspect of the present invention, wherein said volatile dye is to have at a certain temperature to wave
The coloring matter of the property sent out or the combination of coloring matter, include but not limited to non-volatile inorganic dyestuff or organic dyestuff and combinations thereof.
Volatile dye is also referred to as thermo-sensitive material in the present invention.In one embodiment, described volatile dye include but not
It is limited to azo dyes, anthraquinone dyes, compound of formula I or derivatives thereof or a combination thereof.
Method described according to a first aspect of the present invention, wherein said volatile dye is compounds of Formula I:
Wherein,
R1 is selected from hydrogen, halogen, C1-6Straight or branched alkyl, C1-6Straight or branched alcohol ,-COR2 ,-COOR2；
R2 is selected from hydrogen, C1-6Straight or branched alkyl (such as methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, sec-butyl,
The tert-butyl group, n-pentyl, isopentyl, neopentyl, n-hexyl etc.), C1-6Straight or branched alkylamine (such as methyl amine, ethylamine,
N-pro-pyl amine, isopropylamine, n-butylamine, sec-butylamine, tert-butylamine, n-pentyl amine, isoamylamine, neopentyl amine, just oneself
Base amine etc.).
In one embodiment, described R1 is selected from hydrogen, halogen ,-COR2 ,-COOR2, and R2 is selected from hydrogen, C1-4Straight chain or
Alkyl group (such as methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, sec-butyl, the tert-butyl group), C1-4Straight or branched alkylamine
(such as methyl amine, ethylamine, n-pro-pyl amine, isopropylamine, n-butylamine, sec-butylamine, tert-butylamine etc.).An enforcement
In scheme, described R1 is selected from hydrogen ,-COOH ,-COOCH3、-COOCH2CH3、-COOCH2CH2CH3、-COOCH(CH3)2。
Method described according to a first aspect of the present invention, wherein said volatile dye layer can also include one or
Multiple volatilization auxiliary agent, described volatilization auxiliary agent can be easily waving of various controllable pigment or dyestuff evaporation rate and temperature effects thereof
Stimulating food matter.In one embodiment, described volatilization auxiliary agent can be various volatile compounds, include but not limited to straight chain or
Side chain or cycloalkane or aromatic hydrocarbon (including but not limited to naphthalene, anthracene), various straight or brancheds or fragrance or cyclic alcohol (include but do not limit
In erythrol, lauryl alcohol, tridecanol, tetradecyl alchohol, pentadecanol, soft lipidol, Heptadecyl alcohol, stearyl alcohol etc.), various straight or brancheds or
Fragrance or loop chain carboxylic acid (include but not limited to maleic acid, fumaric acid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, Petiolus Trachycarpi
Acid, adipic acid, decanedioic acid, dodecanedioic acid etc.), various aminoacid (include but not limited to amino benzoic Acid, leucine, phenylpropyl alcohol ammonia
Acid etc.), various ester type compounds, various sulfones (include but not limited to sulfobenzide., diphenyl disulfone, dibenzyl sulfone, dibutyl sulfone
Deng), it is also possible to it is various volatile natural materials, includes but not limited to naphthalene, Camphora etc..
Method described according to a first aspect of the present invention, wherein said volatile dye layer is coated on backing material.
In one embodiment, described volatile dye layer is coated on backing material, and it is described to make this backing material stick to
On thermo-responsive article.In one embodiment, described backing material includes but not limited to paper, such as common copy paper, printing
Paper, sticky label paper；Thin polymer film, such as polyethylene, polrvinyl chloride, polypropylene, polystyrene, poly terephthalic acid second two
Alcohol ester etc..In one embodiment, described volatile dye is dissolved in solvent the most coated on described backing material
's.In one embodiment, described solvent includes but not limited to water, and organic solvent such as hexane, hexamethylene, tetrahydrochysene furan
Mutter, benzene, dimethylbenzene, methanol, ethanol, isopropanol, 2-butanol, acetone, diethyl ether, methyl acetate, ethyl acetate, carbon tetrachloride,
Chloroform, dichloromethane, dichloroethanes etc., and combinations thereof.
Method described according to a first aspect of the present invention, wherein said adsorbing material is any can irreversibly to adsorb
The material of described volatile dye.In one embodiment, the speed of described adsorbing material absorption volatile dye is more than
The evaporation rate of volatile dye.In one embodiment, the speed of described adsorbing material absorption volatile dye is long-range
Evaporation rate in volatile dye.In one embodiment, the speed of described adsorbing material absorption volatile dye is remote
Evaporation rate more than volatile dye so that the speed that dyestuff is adsorbed is substantially only relevant with the evaporation rate of dyestuff.?
In one embodiment, the speed of described adsorbing material absorption volatile dye is much larger than the evaporation rate of volatile dye,
The apparent evaporation rate making dyestuff is only affected by temperature (or the heat absorbed), and is not produced by after such as volatilizing because of self
The impact of the factors such as raw saturated/near saturated vapor is hindered.In one embodiment, described adsorbing material include but not
It is limited to oiliness or aqueous adhesive sticker, business self-adhesive paper and adhesive sticker adhesive tape etc..
Method described according to a first aspect of the present invention, wherein said diaphragm seal can make described sorbing material layer and volatilization
Property dye coating seal be attached on described thermo-responsive article.Thus, thermo-responsive article received heat or temperature influence are being monitored
In the case of degree, such as, in storage and/or transportation, volatile dye and adsorbing material are in by described diaphragm seal and heat
The enclosed system that sensitive articles is constituted does not escapes, thus the dyestuff volatilized because of heat amount/variations in temperature is substantially completely
It is adsorbed onto in described adsorbing material.Method described according to a first aspect of the present invention, is wherein terminating the thermo-responsive thing of described monitoring
In the case of product received heat or temperature influence degree, such as after the storage through needing and/or transportation, right
When described thermo-responsive article are further processed (such as use these article, judge whether the quality of these article lost efficacy, etc.),
Described diaphragm seal can be peeled off with thermo-responsive article, optionally make volatile dye layer separate with both sorbing material layers, from
And can observe or measure the dyestuff surplus in volatile dye layer.The color of dyestuff surplus and this volatile dye layer it
Between be proportionate, therefore, in one embodiment, described dyestuff surplus can be by the characterization of this volatile dye layer.
Second aspect present invention provides a kind of method of quality state monitoring thermo-responsive article, and the method includes following
Step:
I () provides thermo-responsive article, determine these thermo-responsive article its expectation dispose (such as preserve and/or transport, or
Accelerated stability test) temperature (can represent with T1 in the present invention) under keep effective quality state energy duration
(can refer in the present invention can lasting maximum duration, also referred to as effect duration, can represent with t1), and the most true
Fixed described thermo-responsive article allow that the heat of absorption (in the present invention can be with Ca (calory) table under keeping effective quality state
Show)；Wherein said effect duration can also determine at a temperature of multiple different expectations are disposed；
(ii) certain area on these thermo-responsive article adheres to one layer of volatile dye (the most non-volatile amount, and now
The priming color amount of dye coating can be expressed as C0)；
According to described thermo-responsive article expectation dispose temperature (T1) and under T1 these thermo-responsive article keep effective quality
State institute can duration (t1), determine the volatile dye layer that C0 measures process under this T1 and t1 Disposal Conditions after this dyestuff
The color theory surplus (now the color theory surplus of dye coating can be expressed as C1) of layer；
(iii) in this volatile dye, one layer of adsorbing material is adhered to；
(iv) adhering to diaphragm seal at above-mentioned certain area and periphery thereof, this diaphragm seal makes described sorbing material layer and volatility
Dye coating seals and is attached on described thermo-responsive article；
Wherein, described volatile dye (such as under the temperature conditions that expectation is disposed, such as, is being expected under heating condition
Storage and/or transport temperature conditions under, such as disposing in the case of temperature surprisingly raises, such as, expecting in accelerated test
Disposal temperature conditions under, such as in the case of accelerated test desired disposal temperature is 25 DEG C and/or 37 DEG C) can volatilize,
Described adsorbing material irreversibly adsorbs volatilized dyestuff, and the color of volatile dye layer takes off variable and (is i.e. equivalent to dye
The volatile quantity of material, this color takes off variable and can be expressed as CF, wherein CF=C0-C1 in the present invention) inhaled with thermo-responsive article
The being proportionate property of heat received；
V () is in the described thermo-responsive thing having adhered to volatile dye layer, sorbing material layer and diaphragm seal three of step (iv)
Product, through disposing after (the actual storage of such as article and/or transport), make volatile dye layer separate with sorbing material layer, observe or
Measure the actual residual volume of color in volatile dye layer (be now dye coating through the storage of thermo-responsive article reality and/or
Transports etc. process, and the actual residual volume of this color can be expressed as C2):
If now the actual residual volume of the color of dye coating (C2) remains more than or equal to step (ii) described color theory
Amount (C1), then show that described thermo-responsive article are maintained at effective quality state；
If now the actual residual volume of the color of dye coating (C2) is less than step (ii) described color theory surplus (C1),
Then show that described thermo-responsive article are beyond effective quality state.
Method described according to a second aspect of the present invention, the temperature that the expectation of wherein said thermo-responsive article is disposed is this thing
Product are required to dispose the temperature of (such as preserve and/or transport, or Accelerated stability test), e.g. preserve and/or transport
Temperature, e.g. Accelerated stability test desired disposal temperature.Method described according to a second aspect of the present invention, wherein said
Thermo-responsive article keep effective quality state to refer to, and these article still conform to its corresponding quality standard postponing through place.According to this
Method described in invention second aspect, wherein said thermo-responsive article keep effective quality state institute energy duration under T1
(t1) refer to that these article effect duration at temperature T1 is time t1.
Method described according to a second aspect of the present invention, described thermo-responsive article after experience temperature T1 and time t1, its
In the color theory surplus (C1) of the remaining thermo-responsive amount of commodity in effective quality state and dye coating be proportionate.By
This, for concrete thermo-responsive article, it keeps effective quality state (such as to keep active component under the conditions of temperature T1
More than 90%), the time of its experience is above-mentioned time t1, and this time, t1 corresponded essentially to dye coating under the conditions of temperature T1
Time during C1 is turned to by C0 quantitative change.
Method described according to a second aspect of the present invention, is wherein observing or is measuring the color reality in volatile dye layer
During residual volume, it is to compare with the two shade presented of the actual residual volume of color (C2) and color theory surplus (C1)
Relatively.In one embodiment, described color theory surplus (C1) provides with reference color label.An enforcement
In scheme, when observing or measure the actual residual volume of color in volatile dye layer, it is the shade with dye coating and ginseng
Examine what the shade of color label compared.In one embodiment, if the shade of dye coating is than with reference to face
The color of colour code label is deep, then show that described thermo-responsive article still remain in effective quality state；If the color of dye coating is deep
Shallow of light color than reference color label, then show that described thermo-responsive article, beyond effective quality state, have exceeded effect duration the most
Or lost efficacy.In one embodiment, the shade of described reference color label is substantially according to the volatility dye of C0 amount
After the bed of material processes under conditions of T1 and t1, the color theory surplus (C1) of this dye coating determines.
Third aspect present invention provides a kind of monitors the method whether thermo-responsive article lost efficacy, and the method includes following step
Rapid:
1. thermo-responsive article are provided, determine these thermo-responsive article its expectation dispose (such as preserve and/or transport, or
Accelerated stability test) temperature (can represent with T1 in the present invention) under effect duration (can represent with t1 in the present invention)；
Wherein said effect duration can also determine at a temperature of multiple different expectations are disposed；
2. the certain area on these thermo-responsive article adheres to one layer of volatile dye (the most non-volatile amount, and now contaminating
The color ID (that is priming color amount) of the bed of material can be expressed as C0)；
The temperature (T1) disposed according to the expectation of described thermo-responsive article and effect duration (t1) under T1, determine that what C0 measured waves
Hair property dye coating process under this T1 and t1 Disposal Conditions after this dye coating the color theory degree of depth (now dye coating color reason
The opinion degree of depth can be expressed as C1), (its color and shade are substantially to provide a reference color label with this color theory degree of depth
Suitable with color theory degree of depth C1)；
3. in this volatile dye, adhere to one layer of adsorbing material；
4. adhering to diaphragm seal at above-mentioned certain area and periphery thereof, this diaphragm seal makes described sorbing material layer and volatility dye
The bed of material seals and is attached on described thermo-responsive article；
Wherein, described volatile dye (such as under the temperature conditions that expectation is disposed, such as, is being expected under heating condition
Storage and/or transport temperature conditions under, such as disposing in the case of temperature surprisingly raises, such as, expecting in accelerated test
Disposal temperature conditions under, such as in the case of accelerated test desired disposal temperature is 25 DEG C and/or 37 DEG C) can volatilize,
Described adsorbing material irreversibly adsorbs volatilized dyestuff, and the color of volatile dye layer takes off variable and (is i.e. equivalent to dye
The volatile quantity of material, this color takes off variable and can be expressed as CF, wherein CF=C0-C1 in the present invention) inhaled with thermo-responsive article
The being proportionate property of heat received；
5. in the most described thermo-responsive article warp having adhered to volatile dye layer, sorbing material layer and diaphragm seal three of step
After disposing (the actual storage of such as article and/or transport), make volatile dye layer separate with sorbing material layer, observe or measure
The color actual grade of volatile dye layer (is now dye coating through the actual storage of thermo-responsive article and/or transport etc.
Reason, this color actual grade can be expressed as C2):
If now the color actual grade (C2) of dye coating is more than or equal to the step the most described color theory degree of depth (C1),
Or now the color actual grade (C2) of dye coating is more deeper than the color of reference color label or suitable, then show described temperature-sensitive
Sense article are the most effective；
If now the color actual grade (C2) of dye coating is less than the step the most described color theory degree of depth (C1), or this
Time dye coating color actual grade (C2) more shallow than the color of reference color label, then show that described thermo-responsive article have lost
Effect.
Method described according to a third aspect of the present invention, wherein said reference color label and described volatile dye layer one
Rise and be attached on described thermo-responsive article.In one embodiment, described reference color label and described volatile dye layer
Be positioned at adjacent position modes such as () such as label are arranged side by side with dye coating, label wraps dye coating is arranged and together with coated
In a substrate material layer, and this substrate material layer is attached on described thermo-responsive article.In one embodiment, described
Volatile dye layer is coated in a substrate material layer, and this substrate material layer is deep with the color of both reference color labels and color
Spending identical, the most now this substrate material layer can be as a kind of form of reference color label.
Method described according to a third aspect of the present invention, wherein said reference color label and described volatile dye layer one
Rise and be attached on described thermo-responsive article, and reference color label and volatile dye layer are all adsorbed material layer and are covered.
Method described according to a third aspect of the present invention, wherein said reference color label and described volatile dye layer one
Rise and be attached on described thermo-responsive article, and reference color label and volatile dye layer are all adsorbed material layer and are covered,
The most described diaphragm seal makes described sorbing material layer and volatile dye layer, reference color evident seal be attached to described thermo-responsive
On article.In one embodiment, dye coating, reference color label, sorbing material layer and diaphragm seal are being adhered to
Thermo-responsive article, after disposing (the actual storage of such as article and/or transport), make volatile dye layer divide with sorbing material layer
From, the most described reference color label is positioned at adjacent position with described volatile dye layer, and (such as label is with dye coating side by side
Arrange, label wraps dye coating such as arranges at the mode, and this adjacent position is particularly conducive to the two color and/or shade
Naked eyes compare).
Method described according to a third aspect of the present invention, wherein step 5. in, compare volatile dye layer with reference to face
The shade of both colour code label, if the color depth of dye coating is more than or equal to the color depth of reference color label, then
Show that described thermo-responsive article are the most effective；If the color depth of dye coating is less than the color depth of reference color label, then
Show that described thermo-responsive article had lost efficacy.
Fourth aspect present invention provides a kind of time-temperature indicator, and it includes before the use in separate
Indicated work ergosphere and two laminate portion of adsorption function layer, wherein:
Described indicated work ergosphere includes:
Substrate material layer；
Volatile dye layer, it is coated in the side of described substrate material layer；
Optional reference color layer, it is coated in the same side of described substrate material layer with described volatile dye layer, and
And it is positioned at adjacent position with described volatile dye layer, and (such as reference color layer is arranged side by side with volatile dye layer, joins
Examining the modes such as color layers cincture volatile dye layer is arranged, this adjacent position is particularly conducive to naked eyes and compares the two color
And/or shade)；With
First release film layer, it covers on described volatile dye layer and reference color layer；And optional:
Sealant layer, its coated side contrary with described volatile dye layer in described substrate material layer；
Diaphragm seal layer, it covers on described sealant layer；
Non-drying glue layer, it is coated on described diaphragm seal layer；And/or
Second release film layer, it covers on described non-drying glue layer；
Described adsorption function layer includes:
Substrate material layer；
Sorbing material layer, it is coated in the side of described substrate material layer, the most optionally covers on this sorbing material layer
Sealing coat, the size of wherein said sorbing material layer and optional sealing coat is (excellent more than or equal to the size of volatile dye layer
Choosing is more than or equal to the size of both reference color layer and volatile dye layer)；
Non-drying glue layer, it is coated in described substrate material layer and be surrounded on described sorbing material layer and optional isolation
The periphery of layer；With
Release film layer, it covers on described non-drying glue layer and sorbing material layer and optional sealing coat.
In the present invention, in described adsorption function layer, described substrate material layer and described optional sealing coat position respectively
Both sides in described sorbing material layer.
Time-temperature indicator described according to a fourth aspect of the present invention, wherein said indicated work ergosphere and adsorption function
Two laminate portion of layer are before the use in two physically independent laminated sheet material forms.
Time-temperature indicator described according to a fourth aspect of the present invention, it is used for first aspect present invention, second party
Face or the method for the third aspect, with monitor thermo-responsive article received heat or monitor thermo-responsive article quality state or
Monitor whether thermo-responsive article lost efficacy.
Time-temperature indicator described according to a fourth aspect of the present invention, wherein said indicated work ergosphere and adsorption function
Two laminate portion of layer, when using, are peeled off the second optional release film layer, are made indicated work ergosphere be attached to described thermo-responsive
On article, then peel off the first release film layer；Peel off the release film layer on adsorption function layer, make the alignment instruction of adsorbing material layer segment
The volatile dye layer of functional layer part, covers whole indicated work ergosphere by adsorption function layer and is closely covered on described thermo-responsive
On article.
Time-temperature indicator described according to a fourth aspect of the present invention, wherein before described indicated work ergosphere uses,
Dyestuff in volatile dye layer is closed between the first release film layer and substrate material layer.Under this closed state, wave
The property sent out dyestuff will not the effusion of volatilizing because of the change of temperature (such as in the range of-50 DEG C to 50 DEG C).An embodiment
In, before described indicated work ergosphere uses, the dyestuff side in volatile dye layer is closed in the first release film layer, separately
Side is closed in laminated construction, and described laminated construction includes at least one in substrate material layer and following layers: seal
Glue-line, diaphragm seal layer, non-drying glue layer, the second release film layer.First release film layer combines volatile dye layer with laminated construction
Close, can preferably avoid volatile dye to escape, and laminated construction to be indicated work ergosphere more convenient and/or closely pastes
It is overlying on described thermo-responsive article and provides benefit.Such as there is sealant layer, diaphragm seal successively in the side of substrate material layer
In the case of layer, non-drying glue layer and the second release film layer, the second release film layer provides before the use for whole indicated work ergosphere
The environment of one relative closure, after peeling off this second release film layer, the non-drying glue layer wherein exposed again can very convenient and/
Or closely indicated work ergosphere is covered on thermo-responsive article.The most such as sealant layer and diaphragm seal layer can be as substrate materials
Supplementing of the bed of material, prevents volatile dye from escaping.
Time-temperature indicator described according to a fourth aspect of the present invention, wherein said reference color layer is with around waving
The mode of the property sent out dye coating is coated in the same side of described substrate material layer with described volatile dye layer.In the present invention one
In alternative embodiment, the color of reference color layer is identical with the color of substrate material layer and color depth with color depth,
In this embodiment, reference color layer can merge into same layer with substrate material layer, can be not provided with independent the most at this moment
Reference color layer, and the color of substrate material layer and/or color depth can play function and the effect of reference color layer.
Time-temperature indicator described according to a fourth aspect of the present invention, the color of wherein said reference color layer and/or
Color after experience Disposal Conditions of color depth and the dyestuff in volatile dye layer and/or color depth are substantially the same.
Described Disposal Conditions is, at volatile dye layer with sorbing material layer can effectively carry out volatilization-adsorption process of the present invention
(the most described volatile dye under heating condition (such as expectation dispose temperature conditions under, such as desired storage and/
Or under the temperature conditions of transport, such as in the case of disposal temperature surprisingly raises, such as in accelerated test desired disposal temperature
In the case of degree, such as in the case of accelerated test desired disposal temperature is 25 DEG C and/or 37 DEG C) can volatilize, described absorption
Material irreversibly adsorbs volatilized dyestuff, and the color of volatile dye layer takes off what variable and thermo-responsive article were absorbed
Being proportionate property of heat) under conditions of contact time, volatile dye layer experience thermo-responsive article its expectation dispose (such as preserve
And/or transport, or Accelerated stability test) temperature (at least two different temperatures can represent with T1 in the present invention) under
Keep effective quality state duration (can refer to institute's lasting maximum duration of energy in the present invention, also referred to as have
The effect phase, can represent with t1).It is appreciated that thermo-responsive article (such as needing the vaccine 2～8 DEG C of storages) are in its regulation of experience
After effect duration under reserve temperature, (the such as percentage of titer, active component contains the active component of the most remaining effective quality
Amount) amount be equivalent to volatile dye layer and experiencing color shown after above-mentioned T1 and t1 and/or color depth, and this color
And/or color depth is substantially identical with reference color layer.Here it is realize the Main Basis of each purpose of the present invention, and such as this
Invention context describes in further detail, and requires difference according to the use of different thermo-responsive article, and those skilled in the art can
To be readily determined starting color and the degree of depth thereof of volatile dye layer by regulating one or more factors, and with reference to face
The color of chromatograph and the degree of depth thereof, these factors include but not limited to: the kind of volatile dye, composition, consumption, the coated liquid of dyestuff
Formula (solvent wherein used and/or auxiliary agent), the absorption property etc. of adsorbing material.In one embodiment of the present invention
In case, color and/or the difference of color depth between described reference color floor and volatile dye floor can come district by naked eyes
Point.
Time-temperature indicator described according to a fourth aspect of the present invention, wherein said first release film layer be meet with
Any mould release membrance of lower condition: it can be with other layer (such as substrate material layer and optional sealant layer, diaphragm seal layer, no
Drying adhesive layer and the second release film layer) together with volatile dye is sealed in interlayer, dyestuff not reason temperature raise and ease of volatilizing
Go out；It can be peeled off from indicated work ergosphere, makes indicated work ergosphere and adsorption function layer two parts combination patch during to facilitate use
Invest on thermo-responsive article.
Time-temperature indicator described according to a fourth aspect of the present invention, in described indicated work ergosphere, at described substrate
Side contrary with described volatile dye layer on material layer, is disposed with sealant layer, diaphragm seal layer inside-out, does not does
Glue-line and the second release film layer.The most as described above, such as, the second release film layer is whole indicated work to the benefit of this set
Ergosphere provides the environment of a relative closure before the use, and after peeling off this second release film layer, wherein expose does not does
Indicated work ergosphere can very convenient and/or be closely covered on thermo-responsive article again by glue-line.The most such as sealant layer and close
Sealer layer can as substrate material layer supplement, prevent volatile dye from escaping.
Time-temperature indicator described according to a fourth aspect of the present invention, its sorbing material layer and volatility in use
Dye coating directly contacts allows.But in a preferred embodiment, expect to provide separating film layer between which.
The benefit of separating film layer is, can be the space providing physically relative separation between volatile dye layer and sorbing material layer,
The two is avoided directly to contact and cause dyestuff to be adsorbed onto in sorbing material layer in the way of " migration "；Simultaneously at dyestuff because of temperature liter
High and when volatilizing, dyestuff can be freely through this separating film layer and be adsorbed onto rapidly and irreversibly in sorbing material layer.
Time-temperature indicator described according to a fourth aspect of the present invention, sorbing material layer and the chi of optional sealing coat
The very little size more than or equal to volatile dye layer (preferably greater than or equal to reference color layer and the chi both volatile dye layer
Very little).On the one hand the design of this size can be that volatile dye provides more adsorbing material, is the dye of diverse location simultaneously
Material provides homogeneous evaporation rate so that volatile dye layer disposes (such as experience vaccine or medicine at thermo-responsive article through reality
Product storage and/or transportation) a uniform color and luster occurs afterwards, it is beneficial to compare with reference color layer.
Time-temperature indicator described according to a fourth aspect of the present invention, in described adsorption function layer, described substrate material
Bed of material expectation has good mechanical stability, so that thermo-responsive article keep good form in whole actual disposal process
And maintain the function of inner. layers.Additionally, it is desirable to substrate material layer have certain can coated performance or impressionability energy, in order to
Sorbing material layer and non-drying glue layer can be coated onto effectively, or optionally print some product informations in its side or make
Use information.Additionally between expectation substrate material layer and non-drying glue layer there is stronger adhesion property, on the one hand can securely by
Substrate material layer adheres on thermo-responsive article, when needing the most after a procedure to peel off, can make non-drying glue layer and substrate
Material layer is peeled off from thermo-responsive article together with sorbing material layer and optional sealing coat, and is unlikely only peeling liner ground
The bed of material and sorbing material layer remains stick on thermo-responsive article and covers volatile dye layer.
Time-temperature indicator described according to a fourth aspect of the present invention, the non-drying glue layer in adsorption function layer is surrounded on
Described sorbing material layer and the periphery of optional sealing coat, coated in substrate material layer.No matter thermo-responsive article are through actual place
Put how condition changes, expect that non-drying glue layer can be with substrate material layer and the surface of the most thermo-responsive article of thermo-responsive article
Constitute one together and close space, and though dyestuff its whether volatilize and all can not escape into beyond this closing space.Additionally, in order to make
The convenience used, whether when to monitor thermo-responsive article and lose efficacy, this non-drying glue layer and substrate material layer, together with sorbing material layer
Together with optional sealing coat, can easily peel off with thermo-responsive article, and volatile dye layer and reference color layer and
Optional sealant layer, diaphragm seal layer, non-drying glue layer remain adhered on thermo-responsive article, thus can readily pass through naked eyes
Compare both volatile dye layer and reference color layer shade, thus judge to monitor whether thermo-responsive article lost efficacy.
Fifth aspect present invention provides and a kind of uses method described in first aspect present invention, second aspect or the third aspect
The thermo-responsive article of monitoring.
Sixth aspect present invention provides time-temperature indicator monitoring described in a kind of use fourth aspect present invention and is heated
Measure, monitor quality state or monitor whether the thermo-responsive article lost efficacy.
Seventh aspect present invention provides a kind of thermo-responsive article, and it includes thermo-responsive article body, and adheres to it
On time-temperature indicator, described time-temperature indicator includes indicated work ergosphere and two laminate part of adsorption function layer
Point, wherein:
Described indicated work ergosphere includes:
Substrate material layer；
Volatile dye layer, it is coated in the side of described substrate material layer；
Optional reference color layer, it is coated in the same side of described substrate material layer with described volatile dye layer, and
And it is positioned at adjacent position with described volatile dye layer, and (such as reference color layer is arranged side by side with volatile dye layer, joins
Examining the modes such as color layers cincture volatile dye layer is arranged, this adjacent position is particularly conducive to naked eyes and compares the two color
And/or shade)；
Wherein, the side of the bare volatile dye layer of described substrate material layer adheres on described thermo-responsive article,
And optionally include between this substrate material layer and thermo-responsive article:
Sealant layer, its coated side contrary with described volatile dye layer in described substrate material layer；
Diaphragm seal layer, it covers on described sealant layer；And/or
Non-drying glue layer, it is coated on described diaphragm seal layer；
Described adsorption function layer includes:
Substrate material layer；
Sorbing material layer, it is coated in the side of described substrate material layer, the most optionally covers on this sorbing material layer
Sealing coat, the size of wherein said sorbing material layer and optional sealing coat is (excellent more than or equal to the size of volatile dye layer
Choosing is more than or equal to the size of both reference color layer and volatile dye layer)；With
Non-drying glue layer, it is coated in described substrate material layer and be surrounded on described sorbing material layer and optional isolation
The periphery of layer；
Wherein, the described indicated work that described sorbing material layer and optional sealing coat will adhere on described thermo-responsive article
Ergosphere covers；Described non-drying glue layer adheres on described thermo-responsive article, and special with substrate material layer and thermo-responsive article
It is that the surface of thermo-responsive article constitutes a space being closed by indicated work ergosphere together.
Thermo-responsive article described according to a seventh aspect of the present invention, wherein said indicated work ergosphere and two, adsorption function layer
Whether laminate portion combines, for monitoring the received heat of described thermo-responsive article, quality state and/or losing efficacy.
Thermo-responsive article described according to a seventh aspect of the present invention, wherein said indicated work ergosphere and two, adsorption function layer
Laminate portion is before using (i.e. adhering on thermo-responsive article), in two physically independent laminated sheet material shapes
Formula, each of which the most also includes mould release membrance, is beneficial to them and produces, transport and use.Such as, for indicated work ergosphere portion
Point, its both sides each optionally also include the first release film layer described in mould release membrance, such as fourth aspect present invention and/or second release
Film layer；And for example, for adsorption function layer segment, non-drying glue layer therein is optionally closed by release film layer, such as the present invention the 4th
Release film layer described in aspect.Using on thermo-responsive article at described indicated work ergosphere and two laminate portion of adsorption function layer
Time, these mould release membrances are peeled off, such as, peels off the second optional release film layer, make indicated work ergosphere be attached to described thermo-responsive thing
On product, then peel off the first release film layer；Peel off the release film layer on adsorption function layer, make adsorbing material layer segment be directed at indicated work
The volatile dye layer of energy layer segment, covers whole indicated work ergosphere by adsorption function layer and is closely covered on described thermo-responsive thing
On product.
Thermo-responsive article described according to a seventh aspect of the present invention, wherein said reference color layer is to contaminate around volatility
The mode of the bed of material is coated in the same side of described substrate material layer with described volatile dye layer.Real in an alternative of the present invention
Executing in scheme, the color of reference color layer is identical with the color of substrate material layer and color depth with color depth, implements at this
In scheme, reference color layer can merge into same layer with substrate material layer, can be not provided with independent reference face the most at this moment
Chromatograph, and the color of substrate material layer and/or color depth can play function and the effect of reference color layer.
Thermo-responsive article described according to a seventh aspect of the present invention, the color of wherein said reference color layer and/or color
Color after experience Disposal Conditions of the degree of depth and the dyestuff in volatile dye layer and/or color depth are substantially the same.Described
Disposal Conditions is, at volatile dye layer with sorbing material layer can effectively carry out volatilization-adsorption process of the present invention (i.e. institute
State volatile dye under heating condition (such as under the temperature conditions that expectation is disposed, such as in desired storage and/or transport
Temperature conditions under, such as disposing in the case of temperature surprisingly raises, such as in accelerated test desired disposal temperature conditions
Under, such as in the case of accelerated test desired disposal temperature is 25 DEG C and/or 37 DEG C) can volatilize, described adsorbing material is not
Reversibly adsorb the dyestuff that volatilized, and the color of volatile dye layer take off heat that variable and thermo-responsive article are absorbed in
Positive correlation) under conditions of contact time, volatile dye layer experience thermo-responsive article its expectation dispose (such as storage and/or
Transport, or Accelerated stability test) temperature (at least two different temperatures can represent with T1 in the present invention) under maintain
Effect quality state institute can duration (can refer in the present invention the lasting maximum duration of energy, also referred to as effect duration, can
Represent with t1).It is appreciated that thermo-responsive article (such as needing the vaccine 2～8 DEG C of storages) are at its regulation reserve temperature of experience
Under effect duration after, the amount phase of the active component (the such as percentage composition of titer, active component) of the most remaining effective quality
When the color shown after experiencing above-mentioned T1 and t1 in volatile dye layer and/or color depth, and this color and/or color
The degree of depth is substantially identical with reference color layer.Here it is realize the Main Basis of each purpose of the present invention, and as the present invention is upper and lower
Literary composition describes in further detail, and requires difference according to the use of different thermo-responsive article, and those skilled in the art can be by adjusting
Save one or more factors and be readily determined starting color and the degree of depth thereof of volatile dye layer, and the face of reference color layer
Color and the degree of depth thereof, these factors include but not limited to: the kind of volatile dye, composition, consumption, the formula of the coated liquid of dyestuff
(solvent wherein used and/or auxiliary agent), the absorption property etc. of adsorbing material.In one embodiment of the invention,
Color and/or the difference of color depth between described reference color layer and volatile dye layer can be distinguished by naked eyes.
Thermo-responsive article described according to a seventh aspect of the present invention, in described indicated work ergosphere, at described backing material
Side contrary with described volatile dye layer on layer, is disposed with sealant layer, diaphragm seal layer, adhesive sticker inside-out
Layer, indicated work ergosphere the most optionally included the second release film layer before adhering on thermo-responsive article.The benefit of this set is
As described above, such as, the second release film layer is the ring that whole indicated work ergosphere provides a relative closure before the use
Border, after peeling off this second release film layer, the non-drying glue layer wherein exposed very convenient and/or closely can will indicate again function
Laminating is overlying on thermo-responsive article.The most such as sealant layer and diaphragm seal layer can as substrate material layer supplement, prevent from waving
The property sent out dyestuff effusion.
Thermo-responsive article described according to a seventh aspect of the present invention, its sorbing material layer and volatile dye layer in use
Directly contact is allowed.But in a preferred embodiment, expect to provide separating film layer between which.Isolating membrane
The benefit of layer is can be the space providing physically relative separation between volatile dye layer and sorbing material layer, it is to avoid two
Person directly contacts and causes dyestuff to be adsorbed onto in sorbing material layer in the way of " migration "；Wave because temperature raises at dyestuff simultaneously
When sending out, dyestuff can be freely through this separating film layer and be adsorbed onto rapidly and irreversibly in sorbing material layer.
Thermo-responsive article described according to a seventh aspect of the present invention, the size of sorbing material layer and optional sealing coat is more than
Or the size (preferably greater than or equal to reference color layer and the size both volatile dye layer) equal to volatile dye layer.This
On the one hand the design planting size can be that volatile dye provides more adsorbing material, and the dyestuff for diverse location provides simultaneously
Homogeneous evaporation rate is so that volatile dye layer disposes (such as experience vaccine or drug storage at thermo-responsive article through reality
And/or transportation) a uniform color and luster occurs afterwards, it is beneficial to compare with reference color layer.
Thermo-responsive article described according to a seventh aspect of the present invention, in described adsorption function layer, described substrate material layer
Expect that there is good mechanical stability, so that thermo-responsive article keep good form in whole actual disposal process and tie up
Hold the function of inner. layers.Additionally, it is desirable to substrate material layer have certain can coated performance or impressionability energy, in order to absorption
Material layer and non-drying glue layer can be coated onto effectively, or optionally print some product informations in its side or use letter
Breath.Additionally there is between expectation substrate material layer and non-drying glue layer stronger adhesion property, on the one hand can be securely by substrate
Material layer adheres on thermo-responsive article, when needing the most after a procedure to peel off, can make non-drying glue layer and backing material
Layer is peeled off from thermo-responsive article together with sorbing material layer and optional sealing coat, and is unlikely only peeling liner bottom material layer
And sorbing material layer remains stick on thermo-responsive article and covers volatile dye layer.
Thermo-responsive article described according to a seventh aspect of the present invention, the non-drying glue layer in adsorption function layer is surrounded on described suction
Enclosure material layer and the periphery of optional sealing coat, coated in substrate material layer.No matter thermo-responsive article are through actual Disposal Conditions
How to change, expect non-drying glue layer can together with the surface of substrate material layer and the most thermo-responsive article of thermo-responsive article structure
Become one to close space, and though dyestuff its whether volatilize and all can not escape into beyond this closing space.Additionally, in order to use
Convenient, whether when to monitor thermo-responsive article and lose efficacy, this non-drying glue layer and substrate material layer, together with sorbing material layer with optional
Sealing coat together, can easily peel off with thermo-responsive article, and volatile dye layer and reference color layer and optional
Sealant layer, diaphragm seal layer, non-drying glue layer remain adhered on thermo-responsive article, thus readily can be compared by naked eyes and wave
Both the property sent out dye coating and reference color layer shade, thus judge to monitor whether thermo-responsive article lost efficacy.
Eighth aspect present invention provides compound of formula I:
Wherein,
R1 is selected from hydrogen, halogen, C1-6Straight or branched alkyl, C1-6Straight or branched alcohol ,-COR2 ,-COOR2 etc.；
R2 is selected from hydrogen, C1-6Straight or branched alkyl (such as methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, sec-butyl,
The tert-butyl group, n-pentyl, isopentyl, neopentyl, n-hexyl etc.), C1-6Straight or branched alkylamine (such as methyl amine, ethylamine,
N-pro-pyl amine, isopropylamine, n-butylamine, sec-butylamine, tert-butylamine, n-pentyl amine, isoamylamine, neopentyl amine, just oneself
Base amine etc.) etc..
Compound according to a eighth aspect of the present invention, wherein,
R1 is selected from hydrogen ,-COR2 ,-COOR2；
R2 is selected from hydrogen, C1-4Straight or branched alkyl (such as methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, sec-butyl,
The tert-butyl group), C1-4Straight or branched alkylamine (such as methyl amine, ethylamine, n-pro-pyl amine, isopropylamine, n-butylamine, Zhong Ding
Base amine, tert-butylamine etc.) etc..
Compound according to a eighth aspect of the present invention, wherein R1 is selected from hydrogen ,-COOH ,-COOCH3、-COOCH2CH3、-
COOCH2CH2CH3、-COOCH(CH3)2Deng.
Ninth aspect present invention provides compound of formula I described in eighth aspect present invention in preparation for monitoring thermo-responsive thing
Purposes in the received heat of product, monitoring quality state and/or the reagent whether lost efficacy.
Ninth aspect present invention additionally provides compound of formula I described in eighth aspect present invention in preparation for the present invention first
The purposes of the volatile dye of method described in aspect, second aspect or the third aspect.
Ninth aspect present invention additionally provides compound of formula I described in eighth aspect present invention in preparation for the present invention the 4th
The purposes of the volatile dye layer of time-temperature indicator described in aspect.
Ninth aspect present invention additionally provides compound of formula I described in eighth aspect present invention in preparation for the present invention the 7th
The purposes of the volatile dye layer of thermo-responsive article described in aspect.
The most described purposes, wherein said compound of formula I optionally helps with one or more volatilizations
Agent is applied in combination, and described volatilization auxiliary agent can be the volatile of various controllable pigment or dyestuff evaporation rate and temperature effects thereof
Material.In one embodiment, described volatilization auxiliary agent can be various volatile compounds, includes but not limited to straight chain or props up
Chain or cycloalkane or aromatic hydrocarbon (including but not limited to naphthalene, anthracene), various straight or brancheds or fragrance or cyclic alcohol (include but not limited to
Erythrol, lauryl alcohol, tridecanol, tetradecyl alchohol, pentadecanol, soft lipidol, Heptadecyl alcohol, stearyl alcohol etc.), various straight or brancheds or virtue
Fragrant or loop chain carboxylic acid (includes but not limited to maleic acid, fumaric acid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, Petiolus Trachycarpi
Acid, adipic acid, decanedioic acid, dodecanedioic acid etc.), various aminoacid (include but not limited to amino benzoic Acid, leucine, phenylpropyl alcohol ammonia
Acid etc.), various ester type compounds, various sulfones (include but not limited to sulfobenzide., diphenyl disulfone, dibenzyl sulfone, dibutyl sulfone
Deng), it is also possible to it is various volatile natural materials, includes but not limited to naphthalene, Camphora etc..
The most described purposes, wherein said compound of formula I is dissolved in solvent, is used further to monitoring
Described received heat, quality state and/or the reagent whether lost efficacy, or the method for various aspects of the present invention, or be used for
The time-temperature indicator of the present invention or thermo-responsive article, such as by coated at described lining for the compound of formula I that is dissolved in solvent
On bottom material.In one embodiment, described solvent includes but not limited to water, and organic solvent such as hexane, hexamethylene
Alkane, oxolane, benzene, dimethylbenzene, methanol, ethanol, isopropanol, 2-butanol, acetone, diethyl ether, methyl acetate, ethyl acetate,
Carbon tetrachloride, chloroform, dichloromethane, dichloroethanes etc., and combinations thereof.
The feature that any embodiment of either side of the present invention or this either side is had is equally applicable to other
One side or any embodiment of this other either side, as long as they will not be conflicting, be suitable for certainly each other
Time, if necessary can make individual features suitably to modify.
It is further described with feature the most to various aspects of the present invention.
All documents recited in the present invention, their full content is incorporated herein by, and if these literary compositions
Offer expressed implication and the present invention inconsistent time, be as the criterion with the statement of the present invention.Additionally, the present invention use various terms and
Phrase has and well known to a person skilled in the art general sense, nonetheless, the present invention remain desirable at this these terms and
Phrase is described in more detail and explains, the term mentioned and phrase are if any inconsistent with common art-recognized meanings, with institute of the present invention table
The implication stated is as the criterion.
As described herein, term " thermo-responsive article " may refer to any article of case of thermal instability, the most such as
Need-40 DEG C to 50 DEG C storage and/or transport any article (storage time in this temperature range can be 1 hour extremely
Scope between 10 years), preferably need, at-30 DEG C to 40 DEG C of storages and/or the article of transport, preferably to need at-30 DEG C
To 30 DEG C of storages and/or the article of transport, preferably need, at-20 DEG C to 20 DEG C of storages and/or the article of transport, preferably to need
Such as to need at-10 DEG C to 10 DEG C of storages and/or the article of transport at-20 DEG C to 10 DEG C of storages and/or the article of transport,
Such as need at 0 DEG C to 10 DEG C of storage and/or the article of transport, such as, to need at 2 DEG C to 8 DEG C of storages and/or the article of transport.
It can be such as existing any needs at 2 DEG C to 8 DEG C of storages and/or the article of transport, particularly vaccine, biological product,
Biological activity sample, medicine, food, beverage etc..The most presently commercially available any vaccine, biological product, biological activity sample,
Medicine, such as 2005 versions or the version Pharmacopoeia of the People's Republic of China in 2010, two or three contained any needs
At 2 DEG C to 8 DEG C of storages and/or the article of transport.Although some article, such as some medicine, it is indicated in 2 DEG C to 8 DEG C storages
Effect duration is 2 years, and it is as the thermo-responsive article of the present invention, can because of heat absorption decay after placing under the conditions of higher than 8 DEG C, but
It will be appreciated by those skilled in the art that this medicine strictly also can have a certain degree of declining equally 2 DEG C to 8 DEG C of storages because of heat absorption
Become, although low temperature decay degree can be less than the decay temperature under higher temperature.Inventor is expected that by the inventive method and monitors
Thermo-responsive article are the heat effect of cumulative contact in storage and/or transportation, such as the effect duration of 2 DEG C to 8 DEG C of storages
Being the medicine of 2 years, the heat effect exposed by 2 DEG C to 8 DEG C of storages adds up with the heat effect of exposure under higher temperature, with this
Bright described dyestuff volatile quantity characterizes this heat effect and adds up, and then judges that thermo-responsive article are in actual storage and/or transport
During whether beyond its prespecified effect phase standard.
As described herein, term " received heat " is also referred to as " caloric receptivity ", or thermo-responsive article contact with ambient temperature
The accumulative heat absorbed.As described above, it can take off variable by the color of volatile dye layer and/or color takes off variable Rate
Characterize.In one embodiment, this color takes off variable and can use aberration Δ E further* abChange characterize；An embodiment party
In case, the color of volatile dye layer takes off variable Rate can be by the chromatic aberration scope set divided by reaching described chromatic aberration scope
Required time representation；In one embodiment, color takes off variable Rate variation with temperature obeys Arrhenius equation, can
With with the activation energy obtained by the equationaCharacterize.Additionally, received heat of the present invention also can preserve bar by article accordingly
Under part, the loss amount of active component characterizes.Or, received heat of the present invention also can be by the temperature of article and storage time
Product effect determine, such as some article, be equivalent to preserve 4 weeks at 25 DEG C at 5 DEG C of heats of being absorbed for 2 years of storage
The heat absorbed, under the conditions of such two kinds, the loss amount of active component is also suitable.Therefore, in the present invention, term " is subject to
Heat " can reflect whether thermo-responsive article activity/titer after the storage traffic condition that experience is concrete is in product standard institute
The effective status (such as active component content is still more than 90%) of regulation.
As described herein, term " on thermo-responsive article " can refer to outer surface or the inner surface of these thermo-responsive article, excellent
Choosing refers to the outer surface of these thermo-responsive article, the level package of such as vaccine, medicine etc. (or minimum package, such as one ampoule bottle
Vaccine) outer surface, the vaccine of such as glass bottle or the vial outer surface of medicine, or the blood plasma of packed in flexible pouchy,
The soft bag outer surface of milk.
As described herein, term " certain area " refers to a certain region on these thermo-responsive article, the position in this region
It is not particularly limited, but for purposes of the present invention, it is more uniform that this region is contemplated to be ratio, to avoid each material of the present invention
Functional layer attaches irregular when being attached on thermo-responsive article and causes volatile dye to escape.Such as, for vial bag
The thermo-responsive article of dress, this certain area is expected to the uniform part of bottle, and undesirably in bending place, such as this certain area
It is positioned at the usual labelled place of people, and is undesirably positioned at bottleneck, bottleneck etc..Additionally, the size of this certain area is also
It is not particularly limited, but for purposes of the present invention, 0.2～20cm2, it is common that preferably, more preferably 0.5～5cm2, more excellent
Select 0.5～4cm2, more preferably 0.5～2.5cm2, more preferably 0.5～1cm2。
As described herein, term " adheres to ", such as, mentioning that " certain area on these thermo-responsive article adheres to one layer
Volatile dye " time, should " attachment " can be coated get on；Can also is that stick-on；Can also be that printing is got on；
Can also is that on the most manual placement, adhered to by another functional layer fixing the most again.Similarly, term " coated " can also have
Various ways, such as but not limited to blade coating mode, spin coating mode, spraying method, mode of printing etc..Equally, term also " adheres to "
Can there is various ways, the mode etc. that the mode adhered to such as but not limited to adhesive or overlay film cover.
As described herein, term " volatile dye " as the major function material realized used by the object of the invention it
One, it can be that one or more have volatile coloring matter, including Organic substance and inorganic matter arbitrarily theoretically.For
The object of the invention, particularly preferred " volatile dye " of the present invention is to have the coloring matter that fusing point is at 0 DEG C to 80 DEG C, excellent
Selecting fusing point is 10 DEG C to 80 DEG C, and preferably fusing point is 20 DEG C to 80 DEG C, and preferably fusing point is 30 DEG C to 80 DEG C, preferably fusing point be 30 DEG C extremely
60 DEG C, preferably fusing point is 40 DEG C to 80 DEG C, and preferably fusing point is 40 DEG C to 60 DEG C, and preferably fusing point is 50 DEG C to 80 DEG C.Such as at this
The fusing point of some dyestuffs used in invention is 30 DEG C to 60 DEG C, particularly 40 DEG C to 60 DEG C.In the present invention, volatile dye
Particularly fusing point is at the dyestuff of 0 DEG C to 80 DEG C, its less than fusing point and higher than melting temperature under be respectively provided with certain volatility, so
And it will be appreciated by those skilled in the art that more weak less than volatility at a temperature of fusing point, after higher than fusing point, its volatility increases greatly
Add, and rate of volatilization obeys Arrhenius equation.
Such as, if to monitor the epidemic disease needing to reach at 2-8 DEG C of shelf life (activity keeps more than 90%) 2 years by regulation
Seedling, if using fusing point to be about the volatile dye of 40 DEG C, under 2-8 DEG C of temperature conditions, volatile dye has and waves more slowly
Send out.Based on this principle, the primary quantity (i.e. can be described as color depth, C0) that dyestuff uses can be set, this primary quantity is sealed in
Including in the closed system of adsorbing material, then they are placed under 2-8 DEG C of temperature conditions placement 2 years, volatile dye layer
Residual dye amount (also referred to as color theory surplus or color depth, C1) as the reference color degree of depth of the present invention, can
To make a reference colour atla based on this reference color degree of depth, such as reference color layer described in fourth aspect present invention；If waved
After the property sent out dye coating experiences the storage/transportation of reality with this vaccine, the dye coating actual color degree of depth is compared to reference
If deeper or suitable for color depth, then show vaccine after above-mentioned actual storage transport the most before the deadline, if dye
If the bed of material actual color degree of depth is more shallow compared to for the reference color degree of depth, then show that vaccine is after above-mentioned actual storage transport
May lose efficacy because being heated and activity is reduced to less than 90%.Can be with the simplest, cheap side by the inventive method
Formula assert the quality of vaccine, it is to avoid lost efficacy but product the most before the deadline enters and makes from the production time
Use link.Above-mentioned prepare reference colour atla during, use volatile dye to experience the heat effect of 2 years, this area at 2-8 DEG C
Technical staff can also determine the color depth of reference colour atla, example according to existing knowledge by suitably rising the high-temperature shortening time
As used accelerated test known to pharmaceutical field technical staff, such as these methods be recorded in pertinent texts (for example, see
Physical chemistry teaching and research room of University Of Tianjin compiles, physical chemistry, People's Education Publishing House, and 1979；Su Desen, etc., physical pharmaceutics, change
Industrial publishing house, Beijing, 2004；Xi Nianzhu, pharmaceutics, the third edition, People's Health Publisher, Beijing, with thing in 1994 grades
The content of matter such as medicine stability related Sections).Such as make reference to the text-book (Xi Nianzhu, pharmaceutics, the third edition, people's health
Publishing house, Beijing, 1994, p141) the routine test method described in, if the vaccine of 2 years above-mentioned 2-8 DEG C of effect duration is put at 25 DEG C
When putting 8 weeks, activity drops to the standard gauge of 90% and fixs limit, then can set the primary quantity (C0) that dyestuff uses, by close for this primary quantity
It is encapsulated in the closed system including adsorbing material, then they is placed at 25 DEG C and places 8 weeks, the remaining dye of volatile dye layer
Doses (C1), as the reference color degree of depth of the present invention, can make reference colour atla, this mode based on this reference color degree of depth
Determining that the color depth of reference colour atla adds the mode of 2 years compared to 2-8 DEG C can be faster.(the Xi Nian further, it is also possible to make reference to the text-book
Zhu, pharmaceutics, the third edition, People's Health Publisher, Beijing, 1994, p141) above-mentioned ginseng is determined through bent constant temperature method described in
Colorimetric card.The method is typically based on Arrhenius equationIncluding activation energy, speed
The key parameters such as constant k, thermodynamic temperature T.For the thermo-responsive article with certain specific performance, it is possible to use Arrhenius
The principle of equation comprehensively determines volatile dye layer of the present invention and the design requirement of reference color layer of these article applicable, such as
The composition of dye coating and coated concentration, the color depth etc. of reference color layer.Arrhenius equation method will be made further below
Describe in detail.
As described herein, term " adsorbing material " or " sorbing material layer " that formed by it, they can include but not
It is limited to oiliness or aqueous adhesive sticker, business self-adhesive paper and adhesive sticker adhesive tape etc..
As described herein, the term in method described in first aspect present invention, second aspect or the third aspect " seals
Film ", or the term " substrate material layer " in the adsorption function layer of fourth aspect present invention time-temperature indicator, they are can
So that described sorbing material layer and volatile dye layer seal any film layer being attached on described thermo-responsive article.Thus, exist
In the case of monitoring thermo-responsive article received heat or temperature influence degree, such as in storage and/or transportation, volatility
Dyestuff and adsorbing material are in and do not escape in the enclosed system being made up of described diaphragm seal and thermo-responsive article, thus because of heat
Amount/variations in temperature and the dyestuff that volatilizees substantially completely are adsorbed onto in described adsorbing material.In the present invention, term " diaphragm seal "
Or the term " substrate material layer " in adsorption function layer of the present invention, constitutes the material of these diaphragm seals or substrate material layer
Can include but not limited to that paper (such as common copy paper, printing paper, sticky label paper), thin polymer film (such as polyethylene, gather
Vinyl chloride, polypropylene, polystyrene, polyethylene terephthalate etc.) etc..
As described herein, phrase " volatile dye (...) under heating condition can be volatilized " refers to that dyestuff connects with heat
Touching and can volatilize, the speed of volatilization is relevant with the heat intensity contacted, even the reserve temperature specified in thermo-responsive article standard
Under, it also has certain evaporation rate.The highest then evaporation rate of temperature is the fastest, the work of same temperature the most thermo-responsive the highest article
Property/titer reduces the fastest, therefore active or titer the reduction speed of dyestuff evaporation rate and thermo-responsive article is proportionate.
As described herein, term " is maintained at effective quality state " and refers in article are still within effect duration or still
Effective active or titer state, such as certain medicine that the standard of being in specifies specify that the content limit of active component should be labelled amount
More than 90%, then " it is maintained at effective quality state " and refers to that in these article, the content of active component is more than the 90% of labelled amount.Class
As, as described herein, term " beyond effective quality state " refers to that this article quality state does not conforms to the rules, such as certain medicine
Product specify that the content limit of active component should be more than the 90% of labelled amount, then refer in these article " beyond effective quality state "
The content of active component is already below the 90% of labelled amount.
As described herein, term " reference color label " is used for representing a kind of colorimetric card, and its display is in dye described herein
Bed of material color category under color theory surplus and/or the degree of depth, this reference color label can be specifically such as this
Reference color layer in bright indicated work ergosphere.
As described herein, mention whether thermo-responsive article " lost efficacy " and refer to that whether these article are at its effect duration defined
In the range of prescription.Such as a example by the content of active component, certain drug standard specifies that the amount of its active component should be sign
More than the 90% of amount, the most now can according to this medicine after such as preserving and/or transporting its active component whether 90% with
On judge " whether losing efficacy ", if such as active component ＞ 90%, do not lost efficacy, and if active component ＜ 90%; would show lose
Effect.
As described herein, term " expectation is disposed " refers to that described thermo-responsive article need or the process of expectation experience
Journey, the such as storage under standard specifies storage temperatures and/or transport, and the higher of test it is accelerated for some purpose
At a temperature of processing procedure.
As described herein, " reference color label is positioned at adjacent position with described volatile dye layer " is mentioned preferably
Represent that described label is in the same plane with both dye coatings.Further, mention that " label and dye coating are arranged side by side " can
By refer to label and both dye coatings with left and right, left, center, right, up and down, arrange in the way of upper, middle and lower, such as coated with square
Dye coating, on the left of it, right side or side, left and right be provided with label.Further, mention that " setting of label wraps dye coating " is permissible
Referring in coated dye coating periphery also around being coated with dye coating, such as this dye coating is coated is square, and label is arranged
At this square enclosure, it can be square or other shape is as circular.
Polytype time-temperature indicator (TTI) is had to be well known to those skilled in the art.Such as
CN101652645A discloses a kind of time-temperature indicator, and it comprises following time temperature indicator: it comprises at least 1
Metal level or metal-containing layer, and at least 1 doped polymer layer directly contacting described metal level or described metal-containing layer, wherein
Adulterant is acid, alkali or salt or photolatent acid or photolatent alkali, and this adulterant is added into described polymer, and/or at least 1
Polymeric layer, wherein functionalization of polymers has acidity or latent acid alkaline or latent basic group；Or comprise following time-temperature
Indicator, it comprises at least 1 polymeric layer, and this layer contains metallic particles and photolatent acid or photolatent alkali, or at least 1 is gathered
Compound layer, this layer contains metallic particles, and wherein said functionalization of polymers has latent acid or latent basic group.And for example,
CN1914509A discloses a kind of time temperature indicator, and described indicator comprises the finger of at least one the first isomeric forms
Show compound, in valence isomerisation reacts, at the atom or chemical group not having to be connected on described indication compound
In the case of migration, described indication compound changed into described in the second isomeric forms in the way of time and temperature-independent
Indication compound, the formation of wherein said the second isomeric forms can be detected by the physical features of monitoring indication compound
Arrive.But, according to the detailed description of the present invention, and though the time-temperature indicator of the present invention in principle or structure with
And on composition, be different from existing time-temperature indicator the most completely, and the time-temperature indicator of the present invention producing,
The aspect such as cost, simplicity of operation is all highly profitable.Certainly, in order to contribute to the understanding of the present invention, above-mentioned patent literary composition
The full content offered is incorporated herein by.
As described herein, term " lamination " refers to the multiple structure group being superimposed together formed by multiple layer structures
Close.For the time-temperature indicator of fourth aspect present invention, indicated work ergosphere therein and adsorption function layer are before use
It is the most relatively independent two laminate portion.But for the thermo-responsive article of seventh aspect present invention, viscous on it
Attached indicated work ergosphere and two laminate portion of adsorption function layer spatially there is no significantly interval, wherein indicate function
Volatile dye layer in Ceng directly contacts with the sorbing material layer (or if it does, sealing coat) in adsorption function layer, because of
This is for the thermo-responsive article of seventh aspect present invention, with reference to the structure of the time temperature indicator of fourth aspect present invention, and will
Indicated work ergosphere and adsorption function layer are divided into two laminate portion to be intended merely to the convenience described.
As described herein, term " substrate material layer ", for fourth aspect present invention time-temperature indicator and
Speech, all includes this backing material layer laminate at indicated work ergosphere and two part of adsorption function layer, the two laminate portion
Substrate material layer can be identical or different, but it should meet the requirement of each of which for the object of the invention.Such as absorption merit
Substrate material layer in ergosphere, after it is adhered on thermo-responsive article by non-drying glue layer, it should for its inside dye coating and
Sorbing material layer provides an environment sealed, it is to avoid dyestuff evaporate into the outside of this time-temperature indicator.And for instruction
The benefit bottom material layer of functional layer, first it should meet can be by dye print or coated requirement thereon.The present invention's
In one embodiment, backing material or substrate material layer in indicated work ergosphere include but not limited to that paper is (such as common duplicating
Paper, printing paper, sticky label paper), porous or fibrous polymer thin film be (such as polyethylene, polrvinyl chloride, polypropylene, polyphenyl
Ethylene, polyethylene terephthalate etc.) etc..In one embodiment of the invention, the substrate material in adsorption function layer
Material or substrate material layer include but not limited to paper (such as common copy paper, printing paper, sticky label paper), thin polymer film
(such as polyethylene, polrvinyl chloride, polypropylene, polystyrene, polyethylene terephthalate etc.) etc..
As described herein, term " reference color layer " refers to evaluate the dyestuff degree of volatility of volatile dye layer,
The reference color arranged, the colorimetric card arrived as people are commonly used.In the present invention, the color category of reference color layer
Can be identical or different with the color category of volatile dye layer.In one embodiment, the color category of reference color layer
Identical with the color category of volatile dye layer, the benefit that the two color is identical is apparent from, such as, can avoid because of face
Difference in color kind and be difficult to judge or judge by accident the true quality state of thermo-responsive article.In the present invention, if thermo-responsive
It is deeper than reference color that article postpone the color of volatile dye layer through place, then it is assumed that these thermo-responsive article are also in effective quality shape
State, if the color of volatile dye layer is more shallow than reference color, then it is assumed that these thermo-responsive article had lost efficacy.
As described herein, term " mould release membrance " is a kind of film material, indicates at fourth aspect present invention Time-temperature
All using in two function laminations of device, it designs for production and the use of this time-temperature indicator, can make
Other material layer will not be infected with foreign body, can also readily peel off in use.Used by indicated work ergosphere of the present invention first
The release film layer used in release film layer and the second release film layer and adsorption function layer, they can be identical or different, as long as
They are capable of its purpose needed.In one embodiment, the first release film layer is expected it can be avoided that wherein cover
Dyestuff volatilizees.In the present invention, the material used by mould release membrance can extensively select, and nonrestrictive example includes: paper, wax
Paper, thin polymer film (such as polyethylene, polrvinyl chloride, polypropylene, polystyrene, polyethylene terephthalate etc.) etc..
" sealant layer " in indicated work ergosphere is possible to prevent dyestuff penetration to migrate after passing substrate material layer even to volatilize.
Although present invention contemplates that and use the substrate material layer can avoided infiltration, migrate as far as possible, but for the purposes of the present invention, at substrate
The coated sealant layer in side contrary with dye coating on material layer is preferred.The material of fluid sealant or sealant layer is can be wide
General selection, nonrestrictive example includes: commercially available common glue.
Effect with above-mentioned " sealant layer " is similar, and " diaphragm seal layer " in indicated work ergosphere is possible to prevent dyestuff penetration to wear
Migrate after crossing substrate material layer and even volatilize.The material of diaphragm seal or diaphragm seal layer can extensively select, nonrestrictive
Example includes thin polymer film (such as polyethylene, polrvinyl chloride, polypropylene, polystyrene, polyethylene terephthalate etc.)
Deng.
" non-drying glue layer " in indicated work ergosphere or adsorption function layer can be that corresponding material layer provides bonding and closes
Effect." non-drying glue layer " in indicated work ergosphere and two layer of adsorption function layer can be identical or different, but expects absorption merit
" non-drying glue layer " in ergosphere has good sealing property, can make substrate material layer and heat when indicator of the present invention uses
Sensitive articles is combined closely and is formed a closing space that can avoid dye leakage.The material of adhesive sticker or non-drying glue layer is permissible
Extensively selecting, nonrestrictive example includes oiliness or aqueous adhesive sticker, business self-adhesive paper and adhesive sticker adhesive tape etc..
" sorbing material layer " in adsorption function layer be the dyestuff of volatilization in irreversibly absorbing dye layer, expects that it is inhaled
It is not dyestuff evaporation rate speed limit process that attached speed is large enough to make it, and evaporation rate is the most only by the shadow of temperature/heat
Ring.
" sealing coat " in adsorption function layer can be the space providing a buffering between adsorbing material and dye coating, with
It is beneficial to the completing of volatilization-adsorption process of dyestuff.The material of sealing coat can extensively select, nonrestrictive example bag
Include: non-woven fabrics, nylon P6 net, nylon P66 net.
In the present invention, for the substrate material layer of indicated work ergosphere, the concrete material used according to this substrate material layer
Can the most optionally use sealant layer, diaphragm seal layer, non-drying glue layer and the second release film layer.If such as in indicated work
After volatile dye that the side of the substrate material layer in ergosphere is coated, the performance of this substrate material layer be enough to prevent the dyestuff will not
Be diffused into the opposite side of this substrate, then sealant layer, diaphragm seal layer, non-drying glue layer and the second release film layer all may be used；When
So, for the ease of making indicated work ergosphere be combined with thermo-responsive article, non-drying glue layer and the second release film layer can preferably be included.
Certainly, in one embodiment, in the side of substrate material layer, above-mentioned sealant layer, diaphragm seal layer, no are included successively
Drying adhesive layer and the second release film layer.
In the present invention, the non-drying glue layer in adsorption function layer, the substrate material layer in adsorption function layer and thermo-responsive thing
Product three constitutes one together and closes space.Term " closing space " does not expect it is a kind of hole state, but various material
Layer is filled in wherein, forms a lamelliform being substantially in the form of real core and closes space.
According to the present invention, the method for various aspects therein, and provided time-temperature indicator they monitoring time
Between and temperature range can be the most widely, at a certain temperature or in a certain temperature range, time length of its instruction can
Easily to change by such as arranging the color depth of reference color layer, the such as article of storage at being expected to about 5 DEG C,
The time of its instruction can be set to 1 day, 30 days, June, 1 year, 2 years, 3 years etc..The setting of these temperature and times is such as but not
It is limited to: temperature range-20 DEG C to 50 DEG C, 1 hour to 10 years time；Temperature range-10 DEG C to 50 DEG C, 1 hour to 8 years time；
Temperature range 0 DEG C to 50 DEG C, 1 hour to 8 years time；37 DEG C, 1 hour to 50 day；25 DEG C, 5 hours to 1 years；5 DEG C, 1 day to 6
Year.
In the present invention, when mentioning " layer ", it both can refer to certain concrete material layer, it is also possible to refers to this kind of concrete material,
As long as context does not haves contradiction.Such as mention " diaphragm seal layer ", under feasible linguistic context, also referred to as " diaphragm seal ".
In the present invention, mention " the first release film layer " and " the second release film layer ", be not intended that they have any before
Rear or orbution or other relation, and it is intended merely to the convenience described.They are all properly termed as " release film layer " or " release
Film ".
As described herein, term " on thermo-responsive article ", or " the thermo-responsive article " mentioned in similar linguistic context or
" on the packing container of thermo-responsive article " etc., it both can represent thermo-responsive article itself, can also refer to pack this temperature-sensitive
On the packing container of sense article.Such as mentioning " the certain area one layer of volatile dye of attachment on these thermo-responsive article "
Time, refer on these thermo-responsive article or on the packing container having packed thermo-responsive article, adhere to one layer in a certain region and wave
The property sent out dyestuff.It addition, mention " on thermo-responsive article " or " the thermo-responsive article " mentioned in similar linguistic context or " thermo-responsive thing
On the packing container of product " time, inner face or the outside of described " thermo-responsive article " can be referred to, particularly " packed this thermo-responsive thing
The packing container of product " inner face or outside.Such as at container outer surface；Or indicator of the present invention is attached on this container, then
Post a cover layer (this cover layer can be false proof layer or anti-counterfeiting prompting layer) the most again.
In the present invention, mention " quality ", " quality state ", " effectively " of the thermo-responsive article of the present invention, " inefficacy " etc., heat
These situations of sensitive articles both can represent by titer, such as some biological product；Or can represent by activity；All right
Represent with content, the content of such as active component.Their method for expressing is not limited in any way by the present invention.
In the present invention, mentioning the temperature that the expectation of thermo-responsive article is disposed, it can be that a temperature range (is such as store
Hide temperature 2-8 DEG C) or an actual temp (average of above reserve temperature, about 5 DEG C)；An embodiment
In, the temperature that the expectation of thermo-responsive article is disposed is the temperature that at least two is different, and such as one is storage mean temperature 5 DEG C,
One is accelerated test temperature such as 25 DEG C or 37 DEG C.In one embodiment, the temperature that the expectation of thermo-responsive article is disposed is
The temperature that at least two is different, they can be all accelerated test temperature such as 25 DEG C and 37 DEG C.Due to some thermo-responsive article
Although all expecting and/or reserve temperature (such as 5 DEG C) lower effect duration of specifying is identical (time such as titer is down to 90% at them
Between, such as it is 2 years), but they titers at accelerated test temperature such as 25 DEG C are down to the time required for same degree
May be different.The most in the present invention, at the temperature (T1) and t1 thereof of the expectation disposal of at least two thermo-responsive article, C1 is determined
It is useful.
In the present invention, compound of formula I has a following structure:
In one embodiment, in compound of formula I, R1 is respectively-COOCH3、-COOCH2CH3With-COOCH (CH3)2.?
In the present invention, R1 is respectively-COOCH3、-COOCH2CH3With-COOCH (CH3)2Compound can be briefly referred to as dyestuff A, dyestuff
B and dyestuff C.
In the present invention, prepared by the method that compound of formula I can use those skilled in the art to know.For example, it is possible to
It is that raw material passes through halogenating reaction, alkylated reaction or acyl with R1 for hydrogen compound of formula I (in the present invention, it can be described as dyestuff H)
Glycosylation reaction hydrolyzes again or the method such as alcoholysis makes R1 substituent group therein be converted into halogen, C1-6Straight or branched alkyl, C1-6Directly
The group such as chain or branched-chain alcoho ,-COR2 ,-COOR2, R2 therein is as described herein.
Existing time-temperature indicator product is higher due to cost of manufacture, limits it at China and other developing chinas
The popularization and application in vaccine cold chain accumulating monitored over time field in Jia, existing product is also not reaching to color change and temperature thereof simultaneously
Effect fully reflects the level of the individualized time-thermindicator of indicated product thermal stability, and indicator product is made
Preserve at a temperature of rear needs are even lower at-18 DEG C.It is an object of the invention to overcome above-mentioned deficiency, utilize the volatility of material
Matter, by-an adsorption process of being heated-volatilize, makes the time-temperature indicator that integrated cost is cheap.
The purpose of one embodiment of the invention is to reduce making and the use cost of indicator, by using new instruction
Device metachromatic principle realizes.Different from polymer-type, enzyme reaction type and diffused indicator, the present invention utilizes the volatility of material
Matter, by one be heated-volatilize-the dye transfer process adsorbed realizes color and changes.After using new principle, valency can be selected
The material that lattice are cheap, widens the range of choice of material simultaneously significantly, reduces the integrated cost that indicator makes.
The purpose of one embodiment of the invention is to make color change and temperature effects thereof can fully reflect indicated product
Individualized time-the thermindicator of product thermal stability, this personalized indicator can thermo-responsive for a certain kind
The concrete Storage Requirement of article and characteristic design.In one embodiment can be by screening evaporation rate and activation energy thereof
Fully volatile dye or other volatility opaque materials of the indicated product thermal stability of reflection realizes.
The purpose of one embodiment of the invention can be by selected volatile dye or other volatility not
Transparent material adds auxiliary agent, makes dyestuff or material prescription, change evaporation rate and the temperature effects thereof of material, be allowed to abundant
The heat stability of the indicated thermo-responsive article of reflection.
The purpose of one embodiment of the invention is making and the use process green ring of described time-temperature indicator
Protect, can realize by selecting green material nontoxic, harmless, eco-friendly；Further, indicator is by an absorption merit
The thermo-sensitive material of ergosphere active adsorption volatilization, by indicated work ergosphere and effective sealing of adsorption function layer of indicator, it is to avoid
Material volatilization after stain product and packaging thereof, protect the functional part of indicator not by outside contamination simultaneously.
The purpose of one embodiment of the invention is to make the time-temperature indicator that can preserve at normal temperatures, permissible
Realize by the following method: indicated work ergosphere and adsorption function layer two parts of indicator make storage respectively, during use, close two
It is one.Indicated work ergosphere thermo-sensitive material coating or printing after, first with to temperature-sensitive functional material used without adsorbing release
Film phonograph seal preserves, and when indicator pastes product container or surface of package, peels off this diaphragm seal and replaces by adsorbable functional layer.
Indicated work ergosphere and adsorption function layer make storage respectively, it is achieved the room temperature of two funtion parts preserves.
In one embodiment of the invention, it is provided that a kind of low temperature accumulating product is (the most of the present invention thermo-responsive
Article) accumulative received heat monitoring method in storage and transport process, be used for judging product whether in cold chain storage and transport process because being heated
Excessively rotten/inefficacy/inactivation, it is characterised in that: one volatilization based on material character, utilize the suction in material volatilization process
The received heat of heat basis weight products；Its two volatile material used is colored materials；It is three with described coloured volatility material
Material makes a function instruction district, and the material after volatilizing that is heated based on material shifts, and causes the color in function instruction district to occur
Notable change, it is determined that commodity the most effectively or rotten/lost efficacy/inactivation.
In one embodiment of the invention, it is provided that the time-temperature indicator made based on above method, it is special
Levy and be: utilize the volatilization character of material, use the double-decker of an indicated work ergosphere-adsorption function layer, two function parts
Divide and make storage respectively, unite two into one during use, paste the appearance of sample to be monitored (thermo-responsive article the most of the present invention)
Device or surface of package.After the commodity or its packaging needing accumulating under cryogenic use this time-temperature indicator, if
Commodity are exposed on the accumulating temperature of setting after special time in cold chain storage and transport process, and indicator presents obvious color and becomes
Change, thus judge commodity the most effectively or rotten/lost efficacy/inactivation.
In one embodiment of the invention, it is provided that for making the instruction function of above-mentioned time-temperature indicator
The temperature-sensitive functional material of layer, it is characterised in that: volatilizing after material heat absorption, speed and the temperature effects thereof of its volatilization fully reflect institute
The speed indicating product rotten or to lose efficacy and temperature effects thereof, therefore selection and the regulation and control of temperature-sensitive functional material are based on indicated
The thermal stability of product.
In one embodiment of the invention, it is provided that for making the instruction function of above-mentioned time-temperature indicator
The temperature-sensitive functional material of layer, it is characterised in that: this temperature-sensitive functional material can be single material, it is also possible to be different materials
Mixture.
In one embodiment of the invention, it is provided that for making the instruction function of above-mentioned time-temperature indicator
The temperature-sensitive functional material of layer, it is characterised in that: the range of choice of this temperature-sensitive functional material includes but not limited to various meet this
The volatile dye required described in bright any embodiment, such as azo dyes, anthraquinone dyes, compound of formula I and derivative
Thing, or opaque volatile material, such as naphthalene, Camphora etc..In one embodiment, the finger of described time-temperature indicator
Showing the temperature-sensitive functional material mixture of functional layer, especially, in mixture, one or more components can regulate and control temperature-sensitive function material
The evaporation rate of material and temperature effects thereof.
In one embodiment of the invention, it is provided that for making the instruction function of above-mentioned time-temperature indicator
The backing material of layer, it is characterised in that: substrate can be regulated and controled by the selection of backing material or modification and covers a layer temperature-sensitive function
Interaction between material, and then regulate and control evaporation rate and the temperature effects thereof of temperature-sensitive functional material.
In one embodiment of the invention, it is provided that for making the adsorption function of above-mentioned time-temperature indicator
The adsorbing material of layer, it is characterised in that: adsorbing material has strong Irreversible Adsorption effect to thermo-sensitive material, and adsorption rate is much larger than warm
The evaporation rate of quick functional material, it is ensured that temperature-sensitive functional material apparent evaporation rate temperature influence.
In one embodiment of the invention, it is provided that for making the adsorption function of above-mentioned time-temperature indicator
The adsorbing material of layer, it is characterised in that: adsorbing material has Irreversible Adsorption effect to thermo-sensitive material, by selecting different absorption
The color change of material regulation and control time-temperature indicator and temperature effects thereof.
In one embodiment of the invention, it is provided that for making the manufacture method of above-mentioned time-temperature indicator,
It is characterized in that: the substrate of indicated work ergosphere is colourless or white or other is light, indicated work ergosphere substrate applies temperature-sensitive
Functional material, temperature-sensitive functional material color and substrate present bigger colour contrast.
In one embodiment of the invention, it is provided that the manufacture method of described time-temperature indicator, its feature exists
In: before applying or printing, temperature-sensitive functional material dissolved or be distributed in suitable solvent.Further, by solvent species
Select evaporation rate and the temperature effects thereof of regulation and control temperature-sensitive functional material.
In one embodiment of the invention, it is provided that the making storage method of described time-temperature indicator, it is special
Levy and be: after the coating of the thermo-sensitive material of indicated work ergosphere or printing, first with to temperature-sensitive functional material used without adsorbing can
Peel seal film phonograph seal preserves, and when indicator pastes product container or surface of package, peels off this diaphragm seal and uses adsorbable merit
Ergosphere is replaced.Indicated work ergosphere and adsorption function layer make storage respectively, it is achieved two funtion parts preserve at normal temperatures.
In one embodiment of the invention, it is provided that the manufacture method of described time-temperature indicator, its feature exists
In: the functional part of indicated work ergosphere and adsorption function layer can be in close contact, it is also possible to does not contacts.
In one embodiment of the invention, it is provided that the manufacture method of described time-temperature indicator, its feature exists
In: indicated work ergosphere and adsorption function layer unite two into one after effectively seal, protection indicator functional part not by outside contamination,
Avoid material volatilization after stain product or its packaging simultaneously.
In one embodiment of the invention, it is provided that the manufacture method of described time-temperature indicator, its feature exists
In: utilize adsorption function layer to adsorb the thermo-sensitive material of volatilization of being heated, be manually set the diffusion process after thermo-sensitive material volatilization, i.e. become
For the adsorption process of adsorption function layer, thus effectively reduce the apparent evaporation rate of temperature-sensitive functional material by non-in product accumulating environment
The impact of temperature factor, improves the accuracy that product uses.
In one embodiment of the invention, it is provided that the range of application of described time-temperature indicator, its feature exists
In: the temperature range of its instruction is between 0-50 degree Celsius, and the time range of its instruction is different with temperature, typical time range
Under 37 Celsius temperatures between 1 hour-50 days, under 25 degrees Celsius between 6 hours-1 year, 5 degrees Celsius lower 1 day-6 years it
Between.
In one embodiment of the invention, it is provided that the application of described time-temperature indicator, including but not
Be limited to vaccine, biological product and other need the medicine of low temperature accumulating.
In the present invention, indicated work ergosphere and adsorption function layer two parts of indicator make storage respectively, close during use
Two is one, thus can realize preserving and/or transport at room temperature of two funtion parts.Adsorption function layer also has three works simultaneously
With: 1, protection label function position is not by outside contamination；2, material volatilization after stain product and packaging thereof are avoided；3, it is manually set
Diffusion process after thermo-sensitive material volatilization, i.e. becomes the adsorption process of adsorption layer, thus it is apparent effectively to reduce temperature-sensitive functional material
Evaporation rate is affected by non-temperature factor in product accumulating environment, improves the accuracy that product uses.Cold chain is needed with other
The product of accumulating such as low temperature food product etc. is compared, and the time-temperature indicator that the present invention provides fully reflects vaccine or other temperature-sensitive
Packing of sense article, the feature of stability temperature influence.
Implement the present invention's it is crucial that select suitable volatile dyestuff or dye combinations, and can this dyestuff of active adsorption
Or the another kind of adsorbing material of a combination thereof or combination.
Embodiment
The present invention can be conducted further description by following various types of embodiments, but, the present invention's
Scope is not limited to following embodiment.One of skill in the art is it is understood that without departing substantially from the spirit and scope of the present invention
Under premise, the present invention can be carried out various change and modification.The present invention is to the material that arrives and test side used in test
Method carries out generality and/or concrete description.Although by realizing many materials that the object of the invention used and operational approach being
It is known in the art that still the present invention still describes in detail as far as possible at this.
A, the example of time-temperature indicator
The present invention utilizes the volatilization character Production Time-thermindicator of material, by one be heated-volatilize-adsorbed
Journey, it is achieved required color change effect.The present inventor design a kind of exemplary time-temperature indicator structure and
Operation principle is depicted in Fig. 1, Fig. 2 A, Fig. 2 B.
Sectional view shown in Figure 1, wherein depicts a kind of time-temperature indicator of the present invention, and it is by two parts group
Becoming, a part is instruction functional layer 1, and b part is adsorption function layer 2, and two parts make storage respectively, unite two into one during use, viscous
It is attached to container or the surface of package of thermo-responsive article to be monitored.
In indicated work ergosphere 1, one layer of fluid sealant 14 of printing below substrate material layer 10, then it is close to add last layer under it
Sealer 13, stops functional material dye coating to spread to direction, bottom.If the sealing effectiveness of fluid sealant is the best, diaphragm seal 13 can
To be nonessential layer.Republish one layer of adhesive sticker 12 below diaphragm seal 13, and (can be described as in the present invention with release film layer 11
First release film layer) protection.Functional part printing on substrate material layer 10 one layer has the coloured of specific volatile energy
Functional material (dyestuff), as temperature-sensitive functional material, forms the volatile dye layer 15 in the present invention, the color of this dye coating 15
(in figure, navy blue) manifests bigger contrast with the reference color layer 16 (in figure, light blue) of substrate material layer 10 or periphery printing.
The speed of volatile dye volatilization used and temperature effects is rotten with indicated product or the speed that lost efficacy and temperature effect thereof
Should try one's best consistent.The printing of indicated work ergosphere is dried, seals with release film layer 17 and preserves.This release film layer 17 seals also
And to volatile dye used without adsorption, sealing property ensures that indicated work ergosphere can at room temperature store and transport.
In adsorption function layer 2, substrate material layer 20 above prints suitable product information, and (such as this TTI is suitable for
Thermo-responsive type of goods) or indicator use information (such as utilize indicator to judge whether thermo-responsive article lost efficacy at needs
Time the information how to operate).Below substrate material layer 20, corresponding to indicated work ergosphere position, printing or coated one layer
Sorbing material layer 21 can be formed, at sorbing material layer 21 with the adsorbing material of the temperature-sensitive volatile dye of active adsorption volatilization
Periphery printing non-drying glue layer 22, the adsorption function layer 2 then making lamination be formed with release film layer 23 seals and preserves.If needing anti-
Only adsorbing material directly contacts with temperature-sensitive functional material (i.e. volatile dye), it is also possible to below sorbing material layer 21 (i.e.
Away from substrate material layer 20) side make a sealing coat 24 (it is nonessential) again.
Referring back to sectional view shown in Fig. 2 A, wherein depict using and using of a kind of time-temperature indicator shown in Fig. 1
Process.In a of Fig. 2 A, the indicated work ergosphere 1 of this indicator will make respectively, stored and 2 two merit of adsorption function layer
Can laminate portion unite two into one: first peel off the mould release membrance 11 bottom indicated work ergosphere 1, indicated work ergosphere 1 is pasted to be monitored
Thermo-responsive article container or packaging 3 surfaces；Peel off mould release membrance 17 and the mould release membrance of adsorption function layer 2 of indicated work ergosphere 1
23, adsorption function layer 2 part is directed at indicated work ergosphere 1 and pastes thermo-responsive article container to be monitored or packaging 3 surfaces.
Preferred embodiment is shape and size and both the volatile dye layer 15 and reference color layer 16 of sorbing material layer 21
Shape and size are identical or more slightly larger than the latter two, and sorbing material layer 21 and optional sealing coat 24 are the completeest the most as shown in the figure
Both all standing volatile dye layer 15 and reference color layer 16, and the non-drying glue layer 22 of sorbing material layer 21 periphery glues together with it
Attached substrate material layer 20 can adhere on the packing container 3 of thermo-responsive article closely so that substrate material layer 20, does not does
Glue-line 22, packing container 3 three of thermo-responsive article form a space that can remaining each functional layer be sealed.Two functional layers
The selection of backing material and adhesive material ensures that indicated work ergosphere will firmly be bonded to product container or surface of package, and inhales
During attached functional layer bonding, there is suitable firmness, can effectively seal the thermo-sensitive material of indicated work ergosphere printing, it is possible to peel off,
Indicated work ergosphere is not had undesirable effect by stripping process.
During this indicator uses, (figure in the case of the thermo-sensitive material of volatile dye layer 15 volatilizees the most completely
B in 2A), after peeling off adsorption function layer 2, remaining dyestuff (blue) and reference color layer about in volatile dye layer 15
16 (light blue) remain to show obvious color distortion (c in Fig. 2 A), i.e. the color of volatile dye layer 15 compares reference color
Layer 16 is deeper, and the product indicated by reflection is still effective, available.In the situation that the thermo-sensitive material of volatile dye layer 15 volatilizees completely
Under (d in Fig. 2 A), peel off after adsorption function layer 2, in volatile dye layer 15, remaining dyestuff (light blue or colourless) is than it
The color of surrounding reference color layers 16 (light blue) close to or the color ratio of more shallow (e in Fig. 2 A), i.e. volatile dye layer 15
Quite or more shallow, the product that instruction is monitored excessively may go bad because being heated or lose efficacy reference color layer 16.When this m-
In thermindicator, the speed of indicator variable color depends on the evaporation rate of heat sensitive dye material, temperature-sensitive functional material and absorption
Material can screen from organic and/or macromolecular material, carries out suitable modification if desired.
Fig. 2 B observes time-temperature indicator of the present invention in use volatile dye layer 15 He from the angle overlooked
The change procedure of reference color layer 16.Illustrate that the present invention utilizes the volatile performance Production Time-thermindicator of material, by one
Individual-adsorption process of being heated-volatilize, it is achieved the change of indicator feature site color, display uses this time-temperature indicator
Whether product excessively goes bad because being heated or lost efficacy.The making of indicated work ergosphere is to apply or print one layer of tool on backing material
Have specific volatile can coloured functional material (volatile dye the most of the present invention) as temperature-sensitive functional material (a in Fig. 2 B, rise
Dotted state, navy blue square, the volatile dye layer 15 corresponding in Fig. 1), the color of this volatile dye is (dark blue in figure
Color square) (, corresponding to the reference color layer 16 in Fig. 1, it can be for a in Fig. 2 B, light blue circle with reference color layer
Substrate or print color layer) present bigger contrast.
During time-temperature indicator and thermo-responsive article are applied in combination, the color depth of reference color layer 16 is not
Becoming, and the color depth of volatile dye layer 15 can shoal because of heat absorption volatilization, the speed shoaled is influenced by temperature, even
Under thermo-responsive article specify desired temperature, volatile dye layer 15 also has a certain degree of volatilization, such as 2-8 DEG C of storage
Hiding the medicine of 2 years effect phases, this medicine is strictly after 2-8 DEG C of storage 2 years, and volatile dye layer 15 can be because of the slowly volatilization of dyestuff
Gradually shoaling, now its color can be more deeper than reference color layer 16 or slightly deep, show this medicine after 2-8 DEG C of storage 2 years still
It is qualified；Storage time continue extend after, volatile dye layer 15 can because the continuation of dyestuff volatilization and continue to shoal, hereafter its
Color can than reference color layer 16 substantially close to or more shallow, show medicine cross effect duration；This process is also design volatility
A kind of embodiment of the color depth of the material category of dye coating 15 and color depth and reference color layer 16, is the most also situated between
Continued the embodiment of accelerated mode.During indicator uses, when thermo-sensitive material volatilizees the most completely, after peeling off adsorbed film
Remaining thermo-sensitive material and periphery reference color remain to show obvious color distortion, and (blueness is just for the b in Fig. 2 B, intermediate point state
Square deeper compared to the color with reference to light color circle), the product indicated by reflection is the most effectively usable.When thermo-sensitive material continues or complete
After full volatilization, after peeling off sorbing material layer, the color that original volatile dye layer 15 position shows and its periphery reference color layer
Close to (c in Fig. 2 B, terminal state) or more shallow, (d in Fig. 2 B, crosses terminal state to the color at 16 positions, and in figure, white is square
Shape is relative to reference to light color circle), thus indicate monitored product excessively may go bad because being heated or lose efficacy.
The color at B, the making of time-temperature indicator and reference color layer position determines
In some embodiments, for making indicated work ergosphere and the absorption merit of the time-temperature indicator of the present invention
The backing material of ergosphere includes but not limited to common paper (such as common copy paper, printing paper, sticky label paper), polymer thin
Film (such as polyethylene, polrvinyl chloride, polypropylene, polystyrene, polyethylene terephthalate etc.).
In some embodiments, the volatility thermo-sensitive material being used for making time-temperature indicator of the present invention includes respectively
Kind of non-volatile inorganic pigment or organic dyestuff or their compound, as azo dyes, anthraquinone dyes, compound of formula I and
Its derivant, also includes various to regulate and control pigment or dyestuff evaporation rate and the volatile substances of temperature effects, Ke Yishi
Various volatile compounds, include but not limited to straight or branched or cycloalkane or aromatic hydrocarbon (including but not limited to naphthalene, anthracene), respectively
Plant straight or branched or fragrance or cyclic alcohol (includes but not limited to erythrol, lauryl alcohol, tridecanol, tetradecyl alchohol, pentadecanol, palmitin
Alcohol, Heptadecyl alcohol, stearyl alcohol etc.), various straight or brancheds fragrance or loop chain carboxylic acid (include but not limited to maleic acid, fumaric acid,
Lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, Palmic acid, adipic acid, decanedioic acid, dodecanedioic acid etc.), various aminoacid
(including but not limited to amino benzoic Acid, leucine, phenylalanine etc.), various ester type compounds, various sulfones (include but not limited to
Sulfobenzide., diphenyl disulfone, dibenzyl sulfone, dibutyl sulfone etc.), it is also possible to various volatile natural materials, including but do not limit
In naphthalene, Camphora etc..
In some embodiments, the solvent being used for dissolving the temperature-sensitive functional material that the present invention uses includes but not limited to
Water, hexane, hexamethylene, oxolane, benzene, dimethylbenzene, methanol, ethanol, isopropanol, 2-butanol, acetone, diethyl ether, acetic acid first
The organic solvents such as ester, ethyl acetate, carbon tetrachloride, chloroform, dichloromethane, dichloroethanes.
In some embodiments, for making the material of time-temperature indicator adsorption function layer of the present invention, can
To use various commercial adsorbing material or adsorbed film, it is desirable to be that material therefor has strong Irreversible Adsorption to the thermo-sensitive material covering layer
Effect, adsorption rate is much larger than the evaporation rate of temperature-sensitive functional material, it is ensured that the apparent evaporation rate of temperature-sensitive functional material is only by temperature
Degree impact.
After the structure fabrication prototype time-thermindicator shown in Fig. 1, under corresponding constant temperature (such as 5
DEG C, 10 DEG C, 25 DEG C and/or 37 DEG C etc.), use the aberration at colorimetric measurements indicator feature position over time, permissible
Obtain color change and the temperature effects thereof of indicator.
Use tintometer can be by the change digitized of color.When using the change of colorimetric measurements color, first definition one
The colour space such as L*a*b*The colour space (also known as CIELAB color space).In this colour space, L*Represent brightness；a*And b*It is colourity
Coordinate, represents color direction；+a*Represent red direction ,-a*Represent green direction ,+b*Represent yellow direction ,-b*Represent blueness
Direction, center is colourless.Work as a*And b*When value increases and removes from center, color saturation increases.In this colour space, aberration can
With with single numeric representation:
ΔE* ab=[(Δ L*)2+(Δa*)2+(Δb*)2]0.5
Wherein, Δ L*For the change of brightness, Δ a*For the change along RED-GREEN colour axis, Δ b*For along Yellow-Blue color
The change of axle.Use such as tintometer quantification colors such as Minolta CR-310 Chroma Meter, it is possible to quantification color
Difference, is evaluated the colour change function of the time-temperature indicator made.Chromatism measurement is using white substrate such as A4 paper as ginseng
Examine, as aberration Δ E* abDuring ＜ 10, color more or less close to the color of substrate, aberration decline for human eye not further
It is significant, therefore in evaluation procedure, by aberration Δ E* ab=10 as the terminal of variable color.In actual application, aberration terminal can
To define according to practical situation, such as according to concrete thermo-responsive article, Δ E* abCan be set as other value, such as Δ E* ab=
5、ΔE* ab=15, Δ E* ab=20, Δ E* ab=25 and/or Δ E* ab=30 etc..
C, the inventive method or the design of indicator and application are described with instantiation
Embodiment 1:
Use dyestuff A as the thermo-sensitive material of time-temperature indicator, dosing print 2% dyestuff A on common A4 paper
(solvent is ethyl acetate, the amount about 200ug of every square centimeter of coated dyestuff A), can active adsorption dye as indicated work ergosphere
The commercially available self-adhesive paper of material A is placed in above dyestuff A, and makes adhesive sticker towards dye coating, then uses the impermeable sealing of dyestuff
Indicated work ergosphere is sealed by film with the adhesive sticker as adsorption function layer, and is placed in by the sample of sealing under 25 DEG C of constant temperatures.
After placing special time, the color of observed and recorded function marker.Fig. 3 is that indicator is transferred at 25 DEG C of constant temperatures and set to 0-105
Color record after it.After dyestuff A volatilizees completely, almost not leaving any dyestuff vestige under bore hole, instruction functional part is several
It is returned to the primary colors of blank sheet of paper.
Embodiment 2:
Fig. 4 a and Fig. 4 b is the method for reference example 1, uses the time-temperature that dyestuff A makes as temperature-sensitive functional material
Indicator aberration Δ E at different temperatures* abThe change of t in time.With aberration Δ E* ab=10 as the terminal of variable color, permissible
Try to achieve Coloring Time and the speed of this indicator, then can be derived, by Arrhenius equation, the activation that its change procedure is corresponding
97.4kJ/mol (Fig. 5) can be about, thus obtain the characterization parameter of indicator colourshifting process temperature effects.This activation energy is permissible
Well cover the inactivation activation energy scope 73.6～109kJ/mol of the polio vaccine of document report, it is also possible to cover
The inactivation activation energy scope of some other vaccines.
Fig. 6 is the label using this dyestuff to design for a kind of Hepatitis B virus vaccine, the variable color response of TTI of the present invention and vaccine
Activity change is the most completely the same.
Embodiment 3:
By the amount of the temperature-sensitive functional material of regulation indicator function instruction position unit are printing, instruction can be regulated and controled
The total time of device variable color, this can be regulated and controled by the concentration of regulation inking amount or ink in printing process.
Fig. 7 is as temperature-sensitive functional material, the method for reference example 1 with dyestuff A, uses different bodies and phase
With the initial chromatic value of the indicator that inking measures, and colourshifting process at identical temperature.The time that indicator is reached home with
The amount linear (Fig. 8) of the temperature-sensitive functional material of unit are printing.
Embodiment 4:
By changing the Nomenclature Composition and Structure of Complexes of dyestuff, Coloring Time and the temperature effects thereof of indicator can be regulated and controled.Fig. 9 is ginseng
The method examining embodiment 1, uses three kinds of compound of formula I (respectively dyestuff A, B, C) as the temperature-sensitive material of time-temperature indicator
Material, the indicator of making aberration at 50 DEG C is very different over time.With aberration Δ E* ab=10 as variable color
Terminal, in the hope of this indicator Coloring Time at different temperatures and speed, then can be able to be derived by Arrhenius equation
Go out dyestuff B and C to be respectively 122 and 75kJ/mol as thermo-sensitive material, the activation energy that indicator change procedure is corresponding, thus obtain
The characterization parameter of indicator colourshifting process temperature effects.The result of dyestuff A it is different from from the activation energy of above dyestuff B and C,
Dyestuff B and C may be used for design and be suitable for the TTI of other thermo-responsive article, or the combination for different dyes.
Embodiment 5:
In temperature-sensitive functional material printing process, use the modulation indicator that different solvents can be suitable color change and
Its temperature effects.Figure 10 is the method for reference example 1, uses hexamethylene, dichloromethane, methyl acetate, ethanol, acetic acid respectively
Ethyl ester is as solvent printing dyestuff A as temperature-sensitive functional material, and the aberration of indicator is over time at the same temperature.Knot
Fruit shows, uses ethanol as solvent, and the color change of indicator is the fastest；Use hexamethylene and methyl acetate as solvent, refer to
Show that device color change is suitable, slower as solvent than ethanol；Using ethyl acetate as solvent, the color change of indicator is slower
A bit；The thermo-sensitive material printing equivalent as solvent with dichloromethane dramatically increases initial value of chromatism, indicator color change ratio
It is the most slack-off for using other solvent, and in all solvents attempted, color change is the slowest.
Embodiment 6:
In temperature-sensitive functional material printing process, add the modulation indicator that suitable auxiliary agent can be suitable color change and
Its temperature effects.Figure 11 is the method for reference example 1, adds appropriate binding agent EC (i.e. second in the organic solution of dyestuff A
Base cellulose), the indicator of making is chromatic aberration and the relation of time at 80 DEG C.Result shows, adds binding agent (EC in figure
Shown in curve) after, indicator required time of reaching home is the instruction not adding binding agent (curve shown in none in figure)
About 3.5 times of device.With aberration Δ E* ab=10 as the terminal of variable color, can be in the hope of the variable color at different temperatures of this indicator
Time and speed, then activation corresponding to change procedure adding binding agent back pointer can be derived by Arrhenius equation
67kJ/mol can be respectively, compared with the indicator not adding binding agent, also there occurs great changes.
Embodiment 7:
By selecting different adsorbing materials can regulate and control color change and the temperature effects thereof of time-temperature indicator.
Figure 12 is the method for reference example 1, with dyestuff B for temperature-sensitive functional material, selects three kinds of different adsorbing materials (material in figure
1,2,3 be respectively commercially available self-adhesive paper, commercially available aqueous adhesive sticker coating A4 paper, commercially available oiliness adhesive sticker coating A4 paper) make time
M-thermindicator, under identical temperature environment, the indicated work ergosphere aberration speed over time of indicator presents significantly
Difference.
From above-mentioned example, the present inventor, surprisingly, it was found that utilize the volatilization character of material, is subject to by one
Heat-volatilization-adsorption process realizes color change, can the most simply and effectively indicate monitored product the most possible because being subject to
Heat excessively rotten or inefficacy.By screening evaporation rate and the suitable volatile dye of activation energy thereof or other volatility materials
Material, makes the material prescription containing auxiliary agent if desired, can make the personalization of the indicated product thermal stability of fully reflection
Time-temperature indicator.By the adsorption function layer of the one layer of energy active adsorption thermo-sensitive material fabricated above in indicator, and make
Indicated work ergosphere and the adsorption function layer of indicator effectively seal, and can avoid material volatilization after stain product and packaging thereof, with
Time protection indicator functional part not by outside contamination.Further, after utilizing adsorption layer to be manually set thermo-sensitive material volatilization
Diffusion process, i.e. become the adsorption process of adsorption layer, thus effectively reduce the apparent evaporation rate of thermo-sensitive material by product accumulating
The impact of non-temperature factor in environment, improves the accuracy that product uses.Further, indicator is designed to two functions
Part makes respectively, sealed storage, is united two into one by two parts when indicator pastes product container or surface of package again,
Indicator can be realized at room temperature store and transport.
Protection scope of the present invention is not constituted any limitation by above-mentioned exemplary description.All employing equivalents or etc.
The technical scheme that effect is replaced and formed, or use different technique or formula, according to by technical scheme or conception
The time-temperature indicator of preparation, within the scope of all falling within rights protection of the present invention.
Claims (40)
1., for monitoring a time-temperature indicator for the quality state of thermo-responsive article, it includes physics before the use
On in separate indicated work ergosphere with two laminate portion of adsorption function layer, wherein:
Described indicated work ergosphere includes:
First substrate material layer；
Volatile dye layer, it is coated on the side of the first substrate material layer, wherein, dyestuff evaporation rate and the work of thermo-responsive article
The reduction speed of property or titer is proportionate；With
First release film layer, its cover on described volatile dye layer, wherein said substrate material layer and the first release film layer
Size more than described volatile dye layer and described volatile dye layer is sealed in described substrate material layer and first from
Between type film layer；
Described adsorption function layer includes:
Second substrate material layer；
Sorbing material layer, it is coated in the side of the second substrate material layer, and the size of wherein said sorbing material layer is more than volatilization
The size of property dye coating；
Non-drying glue layer, it is coated in described substrate material layer and be looped around the periphery of described sorbing material layer；With
Second release film layer, it covers on described non-drying glue layer and sorbing material layer.
2. the time-temperature indicator of claim 1, wherein said first substrate material layer itself is colourless.
3. the time-temperature indicator of claim 2, wherein, in use, peels off the first release film layer and the second mould release membrance
Layer, is directed at the volatile dye layer of indicated work ergosphere by sorbing material layer, makes adsorption function layer cover whole indicated work ergosphere, will
Sorbing material layer and volatile dye layer are enclosed between described first substrate material layer and the second substrate material layer；Serve as a contrast second
Bottom material layer is covered on described thermo-responsive article.
4. the time-temperature indicator of claim 1, wherein, in use, peels off the first release film layer and the second mould release membrance
Layer, is directed at the volatile dye layer of indicated work ergosphere by sorbing material layer, makes adsorption function layer cover whole indicated work ergosphere, and
Sorbing material layer and volatile material are enclosed between described first backing material and the second backing material；By described first
Substrate material layer is covered on described thermo-responsive article.
5. the time-temperature indicator of any one of claim 1-4, it also comprises and described indicated work ergosphere and described absorption
The reference color label of functional layer independence, the color depth of described reference color label and described volatile dye layer experience and institute
State the color depth after the process that the inefficacy disposal of thermo-responsive article is identical identical.
6. the time-temperature indicator of any one of claim 1-4, wherein, described indicated work ergosphere also includes reference color
Label, described reference color label and described volatile dye layer are arranged adjacent each other in described substrate material layer, described with reference to face
After the process that the color depth of colour code label is identical with described volatile dye layer experience and the inefficacy disposal of described thermo-responsive article
Color depth is identical.
7. the time-temperature indicator of any one of claim 1-4, the substrate material layer of wherein said indicated work ergosphere itself
As reference color label, its color depth is identical with described volatile dye layer experience and the inefficacy disposal of described thermo-responsive article
Process after color depth identical.
8. the time-temperature indicator of claim 1, wherein said thermo-responsive article are selected from vaccine, biological product, biological activity
Sample, medicine, food or beverage.
9. the time-temperature indicator of claim 1, the volatile dye in wherein said volatile dye layer is to have fusing point
At the coloring matter of 0 DEG C to 80 DEG C.
10. the time-temperature indicator of claim 9, the fusing point of wherein said volatile dye is at 50 DEG C to 80 DEG C.
The time-temperature indicator of 11. claim 1, the volatile dye in wherein said volatile dye layer is selected from azo
At least one in class dyestuff, anthraquinone dyes, compound of formula I and derivant thereof or a combination thereof, its compounds of formula I have as
Lower formula:
Wherein,
R1 is selected from hydrogen, halogen, C1-6Straight or branched alkyl, C1-6Straight or branched alkoxyl ,-COR2、-COOR2；
R2 is selected from hydrogen, C1-6Straight or branched alkyl, C1-6Straight or branched alkyl amine group.
The time-temperature indicator of 12. claim 1, also includes that one or more are waved in wherein said volatile dye layer
Sending out auxiliary agent and/or solvent, described volatilization auxiliary agent is selected from one or more of following volatile compounds:
Linear paraffin, branched paraffin, cycloalkane or aromatic hydrocarbon, including naphthalene, anthracene；
Straight or branched or fragrance or cyclic alcohol, including erythrol, lauryl alcohol, tridecanol, tetradecyl alchohol, pentadecanol, soft lipidol, 17
Alcohol, stearyl alcohol；
Straight or branched or fragrance or loop chain carboxylic acid, including maleic acid, fumaric acid, lauric acid, tridecanoic acid, myristic acid, 15
Alkanoic acid, Palmic acid, adipic acid, decanedioic acid, dodecanedioic acid；
Aminoacid, including amino benzoic Acid, leucine, phenylalanine；
Ester；
Sulfone, including sulfobenzide., diphenyl disulfone, dibenzyl sulfone, dibutyl sulfone；
And various volatile natural materials, including naphthalene, Camphora；
Described solvent selected from water, hexane, hexamethylene, oxolane, benzene, dimethylbenzene, methanol, ethanol, isopropanol, 2-butanol, third
One or more in ketone, diethyl ether, methyl acetate, ethyl acetate, carbon tetrachloride, chloroform, dichloromethane and dichloroethanes.
The time-temperature indicator of 13. claim 1, wherein, described adsorbing material can irreversibly adsorb from described volatilization
The dyestuff evaporated in property dye coating.
The time-temperature indicator of 14. claim 13, wherein, the speed of described adsorbing material absorption volatile dye is remote
Evaporation rate more than volatile dye.
The time-temperature indicator of 15. claim 1, wherein before using described thermo-responsive article, peels off sorbing material layer,
Measure the aberration of described volatile dye layer, determine that thermo-responsive article had lost efficacy according to this aberration.
The time-temperature indicator of 16. claim 5, wherein before using described thermo-responsive article, peels off sorbing material layer,
The color of volatile dye layer described in visual observations, if this color is deeper than the color of described reference color label, the most described heat
Sensitive articles not yet lost efficacy；If of light color than described reference color label of this color, then described thermo-responsive article are shown
Through losing efficacy.
The time-temperature indicator of 17. claim 6, wherein before using described thermo-responsive article, peels off sorbing material layer,
The color of volatile dye layer described in visual observations, if this color is deeper than the color of described reference color label, the most described heat
Sensitive articles not yet lost efficacy；If of light color than described reference color label of this color, then described thermo-responsive article are shown
Through losing efficacy.
The time-temperature indicator of 18. claim 7, wherein before using described thermo-responsive article, peels off sorbing material layer,
The color of volatile dye layer described in visual observations, if this color is deeper than the color of described reference color label, the most described heat
Sensitive articles not yet lost efficacy；If of light color than described reference color label of this color, then described thermo-responsive article are shown
Through losing efficacy.
The time-temperature indicator of 19. claim 1, the most in use, in described volatile dye layer and described adsorption material
Also including sealing coat between the bed of material, described sealing coat is before combining between sorbing material layer and the second mould release membrance.
The thermo-responsive article of the time-temperature indicator of 20. 1 kinds of any one using claim 1-19.
The method of 21. 1 kinds of time-temperature indicators prepared for monitoring thermo-responsive article quality state, it includes following step
Rapid:
First backing material is provided；
On the side of the first backing material coat volatile dye, formed volatile dye layer, wherein, dyestuff evaporation rate with
The reduction speed of thermo-responsive article activity or titer is proportionate；
Described volatile dye layer covers the first mould release membrance, thus forms indicated work ergosphere；
And
Second backing material is provided；
The side of the second backing material coats adsorbing material, forms sorbing material layer；
The size of wherein said sorbing material layer is more than the size of volatile dye layer；
The peripheral coating non-drying glue layer of the described sorbing material layer in the second substrate material layer；With
Described non-drying glue layer and sorbing material layer cover the second mould release membrance, described sorbing material layer is enclosed in described second
Between backing material and the second mould release membrance, thus form adsorption function layer.
The method of 22. claim 21, after it further includes at coating volatile dye, coats near volatile dye layer
The step of reference color layer, and its color depth experiences with described volatile dye layer and described thermo-responsive article lost efficacy and dispose
The identical color depth after process is identical.
The method of any one of 23. claim 21-22, wherein said thermo-responsive article are lived selected from vaccine, biological product, biology
Property sample, medicine, food or beverage.
The method of any one of 24. claim 21-22, the volatile dye in wherein said volatile dye layer be have molten
O'clock at the coloring matter of 0 DEG C to 80 DEG C.
The method of 25. claim 24, the fusing point of wherein said volatile dye is at 50 DEG C to 80 DEG C.
The method of any one of 26. claim 21-22, the volatile dye in wherein said volatile dye layer is selected from azo
At least one in class dyestuff, anthraquinone dyes, compound of formula I and derivant thereof or a combination thereof, its compounds of formula I have as
Lower formula:
Wherein,
R1 is selected from hydrogen, halogen, C1-6Straight or branched alkyl, C1-6Straight or branched alkoxyl ,-COR2、-COOR2；
R2 is selected from hydrogen, C1-6Straight or branched alkyl, C1-6Straight or branched alkyl amine group.
The method of any one of 27. claim 21-22, also includes that one or more are waved in wherein said volatile dye layer
Sending out auxiliary agent and/or solvent, described volatilization auxiliary agent is selected from one or more of following volatile compounds:
Linear paraffin, branched paraffin, cycloalkane or aromatic hydrocarbon, including naphthalene, anthracene；
Straight or branched or fragrance or cyclic alcohol, including erythrol, lauryl alcohol, tridecanol, tetradecyl alchohol, pentadecanol, soft lipidol, 17
Alcohol, stearyl alcohol；
Straight or branched or fragrance or loop chain carboxylic acid, including maleic acid, fumaric acid, lauric acid, tridecanoic acid, myristic acid, 15
Alkanoic acid, Palmic acid, adipic acid, decanedioic acid, dodecanedioic acid；
Aminoacid, including amino benzoic Acid, leucine, phenylalanine；
Ester；
Sulfone, including sulfobenzide., diphenyl disulfone, dibenzyl sulfone, dibutyl sulfone；
And various volatile natural materials, including naphthalene, Camphora；
Described solvent selected from water, hexane, hexamethylene, oxolane, benzene, dimethylbenzene, methanol, ethanol, isopropanol, 2-butanol, third
One or more in ketone, diethyl ether, methyl acetate, ethyl acetate, carbon tetrachloride, chloroform, dichloromethane and dichloroethanes.
The method of any one of 28. claim 21-22, the speed of wherein said adsorbing material absorption volatile dye is long-range
Evaporation rate in volatile dye.
The method of 29. 1 kinds of quality state monitoring thermo-responsive article, comprises the following steps:
A () provides thermo-responsive article, described thermo-responsive article lost efficacy after elapsed time t1 at temperature T1 that its expectation is disposed or
Rotten；
Adhere on (b) one or more regions on these thermo-responsive article:
Volatile dye layer, the initial aberration of described volatile dye layer is C0, terminal after elapsed time t1 at temperature T1
Aberration is C1；
Sorbing material layer, described adsorbing material irreversibly absorbs the dyestuff that described volatile dye layer evaporates；
Diaphragm seal layer, described diaphragm seal size is more than described sorbing material layer and the size of described volatile dye layer, by described
Sorbing material layer and volatile dye layer seal and are attached on described thermo-responsive article；
Thermo-responsive article after attachment diaphragm seal are disposed through reality；
Observe or measure the actual aberration C2 in the volatile dye layer postponed through actual place；
The relatively actual aberration C2 and described terminal aberration C1 of volatile dye, if the actual C2 of described dye coating is more than described
Terminal aberration C1, then show that described thermo-responsive article the most effectively or do not go bad；If the actual color of described volatile dye layer
Difference C2 less than or equal to described terminal aberration C1, then shows that described thermo-responsive article had lost efficacy or rotten.
The method of 30. claim 29, wherein, first adheres to described sorbing material layer, then adheres to described volatile dye layer.
The method of 31. claim 29, wherein, first adheres to described volatile dye layer, then adheres to described sorbing material layer, and
Before observing or measuring described actual aberration, sorbing material layer is peeled off with described volatile dye layer.
The method of any one of 32. claim 29-31, the wherein said actual aberration comparing volatile dye layer and described end
Point aberration is carried out by visual observations or carries out by measuring the aberration Δ E*ab of volatile dye layer.
The method of any one of 33. claim 29-31, wherein when being compared by visual observations, preparation has described
The reference color label of terminal aberration, described reference color label is attached on described thermo-responsive article.
The method of 34. claim 33, wherein said reference color label is arranged near described volatile dye layer.
The method of any one of 35. claim 29-31, wherein said thermo-responsive article are selected from vaccine, biological product, life
Thing active sample, medicine, food or beverage.
The method of any one of 36. claim 29-31, wherein said volatile dye is selected from azo dyes, Anthraquinones dye
At least one in material, compound of formula I and derivant thereof or a combination thereof, its compounds of formula I has a below formula:
Wherein,
R1 is selected from hydrogen, halogen, C1-6Straight or branched alkyl, C1-6Straight or branched alcohol ,-COR2、-COOR2；
R2 is selected from hydrogen, C1-6Straight or branched alkyl, C1-6Straight or branched alkyl amine group.
The method of any one of 37. claim 29 31, also includes that one or more are waved in wherein said volatile dye layer
Send out auxiliary agent and/or solvent, described volatilization auxiliary agent at least one or a combination thereof in the following volatile compounds:
Linear paraffin, branched paraffin, cycloalkane or aromatic hydrocarbon, including naphthalene, anthracene；
Straight or branched or fragrance or cyclic alcohol, including erythrol, lauryl alcohol, tridecanol, tetradecyl alchohol, pentadecanol, soft lipidol, 17
Alcohol, stearyl alcohol；
Straight or branched or fragrance or loop chain carboxylic acid, including maleic acid, fumaric acid, lauric acid, tridecanoic acid, myristic acid, 15
Alkanoic acid, Palmic acid, adipic acid, decanedioic acid, dodecanedioic acid；
Aminoacid, including amino benzoic Acid, leucine, phenylalanine；
Ester；
Sulfone, including sulfobenzide., diphenyl disulfone, dibenzyl sulfone, dibutyl sulfone；
And various volatile natural materials, including naphthalene, Camphora；
Described solvent selected from water, hexane, hexamethylene, oxolane, benzene, dimethylbenzene, methanol, ethanol, isopropanol, 2-butanol, third
One or more in ketone, diethyl ether, methyl acetate, ethyl acetate, carbon tetrachloride, chloroform, dichloromethane and dichloroethanes.
The method of any one of 38. claim 29-31, the speed of wherein said adsorbing material absorption volatile dye is long-range
Evaporation rate in volatile dye.
The method of any one of 39. claim 29-31, before being additionally included in the described volatile dye layer of attachment, in described heat
The step of attachment substrate material layer on sensitive articles.
The method of 40. claim 39, wherein said substrate material layer itself is reference color label.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110178976.4A CN102853946B (en) | 2011-06-29 | Monitor thermo-responsive article and add up the method for received heat and the indicator of use thereof | |
| BR112013033371-5A BR112013033371B1 (en) | 2011-06-29 | 2012-06-26 | COMBINATION AND MONITORING METHOD FOR MONITORING THE QUALITY STATUS OF A THERMALLY SENSITIVE ARTICLE |
| PCT/CN2012/077568 WO2013000401A1 (en) | 2011-06-29 | 2012-06-26 | Time-temperature indicator and monitoring method for monitoring quality state of thermally sensitive article |
| KR1020147002602A KR101568099B1 (en) | 2011-06-29 | 2012-06-26 | Time-temperature indicator and monitoring method for monitoring quality state of thermally sensitive article |
| US14/127,410 US9618398B2 (en) | 2011-06-29 | 2012-06-26 | Time-temperature indicator and monitoring method for monitoring quality state of thermally sensitive article |
| EP12803738.9A EP2728328B1 (en) | 2011-06-29 | 2012-06-26 | Time-temperature indicator and monitoring method for monitoring quality state of thermally sensitive article |
| JP2014517420A JP5779715B2 (en) | 2011-06-29 | 2012-06-26 | Time-temperature indicator and monitoring method for monitoring the quality state of a heat sensitive article |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110178976.4A CN102853946B (en) | 2011-06-29 | Monitor thermo-responsive article and add up the method for received heat and the indicator of use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102853946A CN102853946A (en) | 2013-01-02 |
| CN102853946B true CN102853946B (en) | 2016-12-14 |
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Address after: 215123 109, northwest 2 building, 99 Jinji Hu Avenue, Suzhou Industrial Park, Jiangsu. Patentee after: Suzhou Huashi heat sensitive technology Co., Ltd. Address before: 215152 Jianmin Road, East Bridge, Huang Dai Town, Xiangcheng District, Suzhou, Jiangsu 58 Patentee before: SUZHOU HUASHI MATERIAL TECHNOLOGY SERVICE CO., LTD. |